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A Golden Era of Cell-Assisted Neurodevelopment

A Golden Era of Cell-Assisted Neurodevelopment

A Golden Era of Cell-Assisted Neurodevelopment

Adipose Tissue – Fat’s Neurodevelopmental Potential
Here, we explore why an intravenous infusion of a parent’s Adipose-Derived Regenerative Cells (ADRCs), administered under the Federal Right to Try Act of 2017, improved developmental progress in four children with diverse diagnoses. [1] [2]

(Note: Quotes are summarized and lightly edited for clarity.)
Rasmussen’s Encephalitis
“Ann’s imagination has been back in full force. She would play, but it seems she’s more imaginative. Do you agree, Mom? “

“Absolutely, the picture she made yesterday was really original…not the rote pictures of hearts she’s made the last months (love the love in the hearts, but it seemed she didn’t have access to the rest of her experience).”

Disorders of the Corpus Callosum
“Becky is walking all over the place. I let her decide where she is going unless we are running late, and then I hold her hand. She is doing so well.”

Rett Syndrome
“Sally has been very engaged. There are moments throughout the day when she is completely engaged, making eye contact and smiling, and she even finds things funny now.”

Idiopathic Autism
“Ashley is more complimentary and appreciative, overall, more alive!”

Common Symptoms – Different Diagnoses – A New Cell-Assisted Therapeutic Approach

“Autism, or autism spectrum disorder (ASD), refers to a broad range of conditions characterized by challenges with social skills, repetitive behaviors, speech and nonverbal communication,” according to Autism Speaks.

Adipose Tissue and the ADRCs residing within it contain a heretofore well-kept secret that prophesies a new cell therapy-based standard of care for ASD. More on that in a moment; first, let’s demystify developmental disabilities.

Contrary to conventional thought, a growing body of scientific evidence indicates that the Central Nervous System (CNS) alone does not cause ASD symptoms. Instead, researchers connect multiple body systems with developmental delays, seizures, and related health issues.

“Many behaviors and physiologic imbalances are common in secondary or known-cause autism and idiopathic or unknown-cause autism.” (Casanova et al. 2020)[3]

ASD stymies neurologists, pediatricians, and basic scientists for an apparent reason: It involves not just one spectrum but also sub-spectrums, sub-sub-spectrums, and so on.

For example, “Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. There are more than 900 different mutations found on the MECP2 gene, most found in eight different ‘hot spots…’, explains the International Rett Syndrome Foundation.

Yet pharma and biotech focus on their unvaried one drug, one disease (or symptom) model. ASD’s diversity of causes and range of symptoms makes that approach unworkable. Additionally, the prescribed drugs often come with black box warnings, a multitude of potential side effects, and unpredictable interactions. [4] [5] [6]

Contrary to the drug development model, ADRCs are an “adipopharmacy.”

This mixed cell population uses natural intelligence (NI) to reverse the multiple dysregulations that cause the common ASD symptoms. From another angle, we have moved beyond the one-cell does-it-all paradigm. [7] [8] [9]

 

Notably, ADRCs “don’t care” about the cause, e.g., genetic, trauma, environmental, or brain malformation.  Our subcutaneous fat doesn’t express these factors.

“ADRCs are smarter than we are; we just have to get out of the way and let them do their job,” said one prominent stem cell researcher.

HYPOTHESIS – LINKING AT WITH FUNCTIONAL IMPROVEMENT IN ASD

  1. A dissonance of physiologic dysregulations accounts for the common ASD symptoms and comorbidities. [10]
  2. Adipose tissue helps conduct our systemic symphony.
  3. ADRCs play the score by secreting hundreds of trophic (nutritional) factors (the secretome).
  4. The secretome restores multisystem harmony regardless of what instruments or section caused the body’s orchestra to play out of tune, e.g., a genetic mutation, environmental factors, congenital tissue malformations, or a combination thereof.
  5. Through neighboring cell-to-cell communication (the paracrine effect), ADRCs reharmonize the neurochemical imbalances that contribute to brain fog, lack of visual focus, anxiety, depression, seizures, and pain.[11] [12]

Just as music evokes an appropriate emotional response, a trend toward neurochemical balance and multisystem homeostasis, by definition, improves the quality of life for people with ASD-related functional deficits.

Ambrose Cell Therapy for ASD takes advantage of ADRCs’ lead in keeping subcutaneous adipose tissue healthy, even later in life. The fact that we can maintain or gain weight when we are older proves this point. This attribute is undeterred by chronic diseases, genetics, and environmental factors.[13] [14] [15]

ADIPOSE Tissue: The Body’s Pipe Organ—

“In my eyes and ears, the organ is the King of Instruments.”
– Wolfgang Amadeus Mozart

A January 2024 PubMed search discovered over 145,000 papers on the science of adipose tissue. An understanding of the literature concludes that adipose tissue is the “pipe organ” of the body, including the brain.

Like the pipe organ imitates strings, horns, percussion, or wind instruments, adipose tissue (AT) functions as at least three bona fide organs.

  • Endocrine—AT secretes hormones that control nutritional intake, metabolism, sexual function, fertility, immunity, vascular health, and more.

  • Immune – AT contains all the immune cells of the body.

  • Neurologic – AT releases neurochemicals to the brain and other organs. [16]

From another angle, AT contains endothelial cells and endothelial progenitor cells (EPCs), which stimulate blood cell formation and vascular and immune health, all factors that contribute to neurologic health. [17]

In 2001, UCLA and University of Pittsburgh researchers unveiled a pool of multipotent cells in adipose tissue.[18] (Zuk et al. 2001)  More than twenty years of research and over 115,000 publications followed their seminal paper.

Did the investigators imagine their discovery would lead to a brighter future for Ann, Ashley, Sally, Becky, and others with developmental disorders?

Uncommon Causes – A Common Connection

Peer-reviewed literature confirms an unexpected set of factors cause or contribute to ASD functional deficits, seizures, or inappropriate behaviors.

The classical approach to autism spectrum disorders (ASD) is often limited to considering their neuro-functional aspects. However, recent scientific literature has shown that ASDs also affect many body systems and apparatuses such as the immune system, the sensory-motor system, and the gut-brain axis. The connective tissue, a common thread linking all these structures, may have a pathogenetic role in the multisystem involvement of ASD.”  (Zoccante et al Feb. 2022) [19]

Connective tissue supports and protects our body’s systems and organs. However,  connective tissue abnormalities lie at the heart of a wide range of diseases.  In his paper, Dr. Zoccante coined the term “connectiviome” and included ASD in the connective tissue disorder spectrum.

The connectiviome theory begs the question: Can ADRCs that keep adipose connective tissue healthy be repurposed for treating ASD?  But first, what other body systems connect to developmental delays?

THE AUTONOMIC NERVOUS SYSTEM AND THE CONNECTIVEIOME

Autism spectrum disorder (ASD) is associated with atypical autonomic nervous system (ANS) function. (Taylor et al. 2021) [20]

Your autonomic (self-governing) nervous system controls unconscious processes such as breathing, heart rate, blood pressure, muscle control, and bladder and bowel function.

The ANS consists of two nervous systems that supply or restrain nervous energy (innervate):

  • The sympathetic nervous system (SNS) stimulates your fight-or-flight (stress) response.
  • Through the vagus nerve, the parasympathetic nervous system (PNS) inhibits your SNS, allowing you to “rest and digest.”

In other words, the sympathetic and parasympathetic divisions work in concert to stimulate or inhibit various body processes.  Their contrary but complementary functions help maintain whole-body balance or homeostasis, including in the gut.

Our SNS and PNS supply nerves to (innervate) connective tissue, including subcutaneous fat. Therefore, connective tissue health and disease are linked with ANS function or dysfunction.

Therein lies another notable connection between healthy fat and our ADRCs’ potential to retune the autonomic nervous system.

ADRCS RESTORE ANS BALANCE

Before cell therapy, Ashley and Ann displayed aggressive and repetitive behaviors, symptoms of sympathetic nervous system (SNS) hyper-arousal.

Following their intravenous delivery of ADRCs (ADRC-IV), their families shared their girl’s sustained behavioral improvements:

  • “Ashley’s aggressive behavior is gone after her treatment,” says her mom.
  • “Ann’s aunt noticed she wasn’t aggressive like she was before her cell therapy.”
  • Ashley’s mom says she is joining her family and friends in conversations.
  • Sally’s mom says she is “engaged.”

ADRCs and the Second Brain – The Gut Microbiome

Notably, the Vagus Nerve (VN), which extends from the base of the brain to the stomach, regulates the gut-brain axis. Thus, by reactivating the VN (restoring vagal tone), ADRCs also restore gut microbiome homeostasis. [21]

“Ann’s constipation is better,” reported her mother four months after ADRC therapy.

These dramatic behavior changes indicate that their girls’ parasympathetic nervous systems are more in tune with their environment. In addition, ADRCs restored Ann’s brain-gut-adipose-tissue communication pathways.[22]

Autonomic and Autoimmune Dysregulation

Many people believe inflammation is the root of all physical and emotional evils. However, there is more to it than that.

An out-of-control autonomic stress response raises cortisol and adrenaline levels, lighting the inflammation fire. Then, the immune system throws gas on the flames, resulting in autoimmune diseases. [23]

UC Davis Mind Institute studies find that ASD children have reduced immune system regulation, as well as shifts in their gut microbiome. A family history of autoimmune diseases adds fuel to the multisystem dysregulation blaze. [24] [25] [26]

In sum, the connectiviome, autonomic dysfunction, and autoimmune dysregulation disconnect the CNS and other systems of the developmentally delayed. [27] There is still more to the multisystem dysregulation cacophony.

ADSC’s immunomodulation mechanism plays a crucial role. They interact with immune cells, including T cells, B cells, macrophages, and dendritic cells, to modulate the immune response. [28]

Neurochemical Imbalances

The symphony’s conductor directs the musicians so that their performance enlivens our emotions. However, while only one conductor leads a symphony, a group of conductors called neurochemicals orchestrates our brains and peripheral and autonomic nervous systems.

Strikingly, over 40 neurochemicals guide our nervous systems. Then, our nerves direct our muscles and organs.

Research has identified altered neurochemical pathways involved in Rett Syndrome, epilepsy, brain injury, and other diagnoses along the continuum. [29]

“In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology…” (Marotta et al. 2020) [30]

ADIPOSE TISSUE – OUR THIRD BRAIN

The adipose tissue as a third brain (Chaldakov et al. 2009) connects the adipose tissue secretome with neurochemical, ANS, and multisystem harmony.

“Altogether, this may, like neuroendocrinology and neuroimmunology, open a novel field of research, neuroadipobiology. Its development may help humans stay lean, thoughtful, and noble.” (Emphasis added) [31]

The literature suggests that ADRCs harness neuroadipobiology and reverse “irreversible” neurochemistry.

Neurotrophic Factors (NF)

As a conductor directs the orchestra, NFs orchestrate our neurons’ growth, survival, and repair. They feed molecular nutrients to the brain, nervous, vascular, and immune systems. [32]

Examples:

  • Brain-derived neurotrophic factor (BDNF) plays an essential role in neuroplasticity and neurodevelopment.[33]
  • Insulin-like growth factor -1 (IGF-1) helps kids grow.

ADRCs increase NF levels

Ashley was at the 25th percentile of weight for her age, indicative of a lack of IGF-1 (insulin-like growth factor-1). She was also behind in school, suggesting reduced BDNF levels. [34] [35]

Within several months of her cell therapy, Ashley:

  • Weighed in the 95th percentile, or average.[36]
  • Graduated second grade with 100% final exam scores.

Ann’s reading level “improved by a whole grade” in the first five months of sixth grade,” her mom said.

Sally’s BMI (body mass index) was at the 15th percentile before her treatment. Four months after her treatment, she also reached the 95th percentile.

Ashley’s, Ann’s, and Sally’s restored development after extended delays suggests that their respective parents’ ADRCs increased IGF-1, BDNF, and other NFs.

Cell biology literature supports this theory.[37] [38] [39] [40] [41]

Neurotransmitters

Neurotransmitters carry messages from one nerve cell across to the next nerve, muscle, or gland cell, explains the Cleveland Clinic.

Dozens of neurotransmitters riff back and forth, depending on the tone of life’s music, like a jazz quartet in a jam session. Their proper balance creates a sense of well-being, energy, restfulness, excitement, relaxation, and so forth.

Example:

Gamma-aminobutyric acid (GABA) calms. Think of GABA as a mellow tune that helps you relax. On the opposite side of the coin, glutamate plays dance music.   But if the music blares, GABA levels reduce, and glutamate increases.

  • Reduced GABA influences visual perception, which could explain Ashley’s lazy eye and Becky’s lack of visual focus. [42] [43] [44]

After cell therapy, their moms shared:

  • “All this (Becky’s) new eye contact is fabulous.”
  • “Ashley’s lazy eye is gone.” [45] [46]

Neuropeptide Y (NPY) helps harmonize the central and peripheral nervous systems. It plays alongside GABA and glutamate. NPY’s functions include controlling epileptic seizures. Research has shown a significant reduction in NPY levels during the delayed post-seizure recovery (postictal period). [47]

  • Sally had a history of fever-induced seizures (febrile seizures). A month after her ADRC infusion, she caught a high fever and a UTI. This time, “No seizures,” reported her mom.
  • Ten months after Ann received ADRCs, her mother and grandmother noted a significant reduction in seizures, and that when “Ann does have a glitch, she recovers right away. In fact, she talked right through one,” noted her mother.

Lest we undervalue Ann’s dramatic improvement, even if imperfect, several seizures per day or “seizure clusters” increase the risk of sudden unexplained death (SUND) by 2.5 times.[48]

Neuroendocrine hormones

“The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, and stress responsiveness.” (Gore 2010) [49]

Example:

Dopamine, norepinephrine, and epinephrine maintain homeostasis through the autonomic nervous system.

  • Epinephrine (adrenaline), an adrenal hormone, takes over in acute stress. It increases inflammation, raises your heart rate and blood pressure, etc.
  • When the stress subsides, dopamine brings a sense of pleasure and reward.

This continuous balancing act between dopamine and adrenal hormones also plays a role in your fight-or-flight response.

After ADRC therapy:

  • Ann had a setback with her annual flu shot. It took about a week, but her mom messaged, “Ann is back to her bubbly self.”
  • “Ashley is joining conversations. She never did that before,” said her mom.
  • “Sally’s dad dropped something on the floor. She picked it up and handed it back to her dad!”. Her mom said this was the first time Sally had demonstrated initiative with perfect motor control. The family started singing “stem cells, stem cells, stem cells” in recognition of Sally’s new ability.

Neurochemical Summary

ADRCs’ treasure trove of signaling molecules, hormones, growth factors, and neurotrophic factors helps:

  • Rebalance the brain’s neurochemicals.
  • Reduce neuroinflammation and immune dysregulation.
  • Rehabilitate neuroplasticity.
  • Improve ANS function and vagal tone.
  • Improve blood flow and glucose metabolism in the brain. [50]
  • Restore multisystem homeostasis.[51] [52] [53] [54] [55]

Conclusion

Ambrose Cell Therapy has demonstrated with four ASD patients with different diagnoses that a single infusion of a parent’s ADRCs made a profound difference in their developmental progress and quality of life. These strong signals of safety and effectiveness call for continued investigation and therapy under the Federal Right to Try Act of 2017.

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[4] Clarke C, Evans J, Brogan K. Treatment Emergent Violence To Self And Others; A Literature Review of Neuropsychiatric Adverse Reactions For Antidepressant And Neuroleptic Psychiatric Drugs And General Medications. Adv Mind Body Med. 2019 Winter;33(1):4-21.

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[7] Alshoubaki YK et al. Modulation of the Activity of Stem and Progenitor Cells by Immune Cells. Stem Cells Transl Med. 2022 Mar 31;11(3):248-258

[8] Caplan AI. Mesenchymal Stem Cells: Time to Change the Name! Stem Cells Transl Med. 2017 Jun;6(6):1445-1451.

[9] Zenić L et al. Medicinal signaling cells niche in stromal vascular fraction from lipoaspirate and microfragmented counterpart. Croat Med J. 2022 Jun 22;63(3):265-272.

[10] Chugani, Diane C et al. Autism Spectrum Disorders (New York, 2011; online edn, Oxford Academic, 1 Sept. 2012),

[11] Zoccante L et al. The “Connectivome Theory”: A New Model to Understand Autism Spectrum Disorders. Front Psychiatry. 2022 Feb 7;12:794516.

[12] Booth A et al. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig. 2016 Apr 1;26(1):25-42.

[13] Perin EC, Willerson JT. Buying new soul. J Am Coll Cardiol. 2012 Nov 20;60(21):2250-1.

[14] Schmitz C et al. The Composition of Adipose-Derived Regenerative Cells Isolated from Lipoaspirate Using a Point of Care System Does Not Depend on the Subject’s Individual Age, Sex, Body Mass Index and Ethnicity. Cells. 2022 Dec 21;12(1):30.

[15] Trevor, L.V.; Riches-Suman, K.; Mahajan, A.L.; Thornton, M.J. Stromal Vascular Fraction Cells from Individuals Who Have Previously Undergone Radiotherapy Retain Their Pro-Wound Healing Properties. J. Clin. Med. 202312, 2052.

[16] Parimisetty A et al. . Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research. J Neuroinflammation. 2016 Mar 24;13(1):67.

[17] Han J et al. Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood. 2010 Feb 4;115(5):957-64.

[18]Zuk PA et al. Multilineage cells from human adipose tissue: implications for cell based therapies.Tissue Eng. 2001;7:211–27.

[19] Zoccante L et al. The “Connectivome Theory”: A New Model to Understand Autism Spectrum Disorders. Front Psychiatry. 2022 Feb 7;12:794516.

[20] Taylor, E. C., Livingston, L. A., Callan, M. J., Ashwin, C., & Shah, P. (2021). Autonomic dysfunction in autism: The roles of anxiety, depression, and stress. Autism25(3), 744-752

[21] Breit S et al. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018 Mar 13;9:44.

[22] Yi CX, Tschöp MH. Brain-gut-adipose-tissue communication pathways at a glance. Dis Model Mech. 2012 Sep;5(5):583-7.

[23] Bellocchi C et al. The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases. Int J Mol Sci. 2022 Feb 23;23(5):2449.

[24] Wu S et al. Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2015 Aug;55:322-32.

[25] Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2012 Mar;26(3):383-92.

[26] Hughes HK et al. Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders. Front Cell Neurosci. 2018 Nov 13;12:405.

[27] Salari V et al. The Anti-Inflammatory Properties of Mesenchymal Stem Cells in Epilepsy: Possible Treatments and Future Perspectives. Int J Mol Sci. 2020 Dec 18;21(24):9683.

[28] Ceccarelli S et al. Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application. Front Cell Dev Biol. 2020 Apr 17;8:236.

[29] Cetin F H et al. ‘Neurotransmitter Systems in Autism Spectrum Disorder’, Autism Spectrum Disorder – Recent Advances. InTech, Apr. 02, 2015.

[30] Marotta R et al. The Neurochemistry of Autism. Brain Sci. 2020 Mar 13;10(3):163.

[31] Chaldakov G et al. (2009). The adipose tissue as a third brain. Obesity and Metabolism. 5. 94-96.

[32] Kermani P, Hempstead B. BDNF Actions in the Cardiovascular System: Roles in Development, Adulthood and Response to Injury. Front Physiol. 2019 Apr 26;10:455.

[33] Erdoğan, M. & Erbas, Oytun. (2023). The Role of Brain-Derived Neurotrophic Factor in Autism Spectrum Disorder: Current Findings and Future Directions. 10.5772/intechopen.112471.

[34] Kahathuduwa, Chanaka N., et al. “Autism spectrum disorder is associated with an increased risk of development of underweight in children and adolescents: A systematic review and meta-analysis.” Research in Autism Spectrum Disorders94 (2022): 101969.

[35] Erdoğan, M. & Erbas, Oytun. (2023). The Role of Brain-Derived Neurotrophic Factor in Autism Spectrum Disorder: Current Findings and Future Directions. 10.5772/intechopen.112471.

[36] Wrigley S, Arafa D and Tropea D (2017) Insulin-Like Growth Factor 1: At the Crossroads of Brain Development and Aging. Front. Cell. Neurosci. 11:14.

[37] Kerschensteiner M et al. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med. 1999 Mar 1;189(5):865-70.

[38] Clauser et al. Adipose-derived stem cells secrete neurotrophic factors. Annals of Oral & Maxillofacial Surgery 2013 Mar 01;1(2):12

[39] Hofer HR, Tuan RS. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther. 2016 Sep 9;7(1):131. doi: 10.1186/s13287-016-0394-0.

[40] Bagno LL et al. Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function. Cell Transplant. 2016;25(9):1609-1622.

[41] Pak J et al.  (2020) Potential Benefits of  Allogeneic Haploidentical Adipose Tissue-Derived Stromal Vascular Fraction in a Hutchinson–Gilford Progeria Syndrome Patient. Front. Bioeng. Biotechnol. 8:574010.

[42] Blue ME, Naidu S, Johnston MV. Altered development of glutamate and GABA receptors in the basal ganglia of girls with Rett syndrome. Exp Neurol. 1999 Apr;156(2):345-52.

[43] Song C et al. Human Occipital and Parietal GABA Selectively Influence Visual Perception of Orientation and Size. J Neurosci. 2017 Sep 13;37(37):8929-8937.

[44] Braat S, Kooy RF. The GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders. Neuron. 2015 Jun 3;86(5):1119-30.

[45] Zhu F et al. (2019). The GABA receptor GABRR1 is expressed on and functional in hematopoietic stem cells and megakaryocyte progenitors. Proceedings of the National Academy of Sciences. 116. 201906251. 10.1073/pnas.1906251116.

[46] Bhandage AK, Barragan A. GABAergic signaling by cells of the immune system: more the rule than the exception. Cell Mol Life Sci. 2021 Aug;78(15):5667-5679.

[47] McGuire JL et al. Differential Regulation of Neuropeptide Y in the Amygdala and Prefrontal Cortex during Recovery from Chronic Variable Stress. Front Behav Neurosci. 2011 Sep 15;5:54.

[48] Bauman K, Devinsky O. Seizure Clusters: Morbidity and Mortality. Front Neurol. 2021 Feb 16;12:636045.

[49] Gore AC. Neuroendocrine targets of endocrine disruptors. Hormones (Athens). 2010 Jan-Mar;9(1):16-27.

[50] Wang Y, Yu S, Li M. Neurovascular crosstalk and cerebrovascular alterations: an underestimated therapeutic target in autism spectrum disorders. Front Cell Neurosci. 2023 Aug 24;17:1226580.

[51] Lina Badimon, Judit Cubedo, Adipose tissue depots and inflammation: effects on plasticity and resident mesenchymal stem cell function, Cardiovascular Research, Volume 113, Issue 9, July 2017, Pages 1064–1073

[52] Naik S, Larsen SB, Cowley CJ, Fuchs E. Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease. Cell. 2018 Nov 1;175(4):908-920.

[53] Alshoubaki YK et al. Modulation of the Activity of Stem and Progenitor Cells by Immune Cells. Stem Cells Transl Med. 2022 Mar 31;11(3):248-258

[54] Sarlo GL, Holton KF. Brain concentrations of glutamate and GABA in human epilepsy: A review. Seizure. 2021 Oct;91:213-227.

[55] Marotta R et al. The Neurochemistry of Autism. Brain Sci. 2020 Mar 13;10(3):163.

AMBROSE Cell Therapy

Your Right to Try

A Golden Era of Cell-Assisted Fitness

A Golden Era of Cell-Assisted Fitness

A Golden Era of Cell-Assisted Fitness

In Oct 2021, Mary Grace, a 58-year-old adventurer, retraumatized her left knee trekking the Himalayas. Until then, she had surmounted a hospitalizing concussion, sports injuries, constant pain, brain fog, and chronic fatigue to scale new heights. But this incident was different – an air ambulance brought her down the mountain.

Mary Grace exercised her Right to Try AMBROSE Cell Therapy six weeks later. Her two-year patient-reported outcome demonstrates that a Golden Era of Cell-Assisted Fitness has begun.

Over the 24 months following her single Ambrose treatment, Mary Grace resumed hiking, skiing, and open-water swimming in Mexico – against the tide, no less. She took up windsurfing alongside whales, too.

Her training culminated with hiking 75 miles of the Appalachian Trail with a backpack and sleeping in a tent – without injury or relapse.

Here, we tie Mary Grace’s downfall to an unsuspected culprit and explain how her adipose-derived regenerative cells (ADRCs) started her climb back to extraordinary fitness levels. Or, as she says, “I am doing more than I ever had before.”

 Tiger’s Travails

In contrast to Mary Grace’s return to fitness, too many elite athletes like Tiger Woods, fitness fanatics, and weekend warriors resort to surgery, drugs, and devices (the standard of care). But they find themselves resigned to living with limitations and pain.   More on Tiger’s road to retirement despite access to the best surgeons fame can buy later. First, what led to Mary Grace’s fall from grace?

Over Training Syndrome – Too Fit?

Mary Grace’s exercise program embraced the five pillars of physical fitness: (1) body composition, (2) flexibility, (3) muscular strength, (4) muscular endurance, and (5) cardiorespiratory endurance.

Mary Grace should have been a pillar of health as she approached her sixties, a pivotal point in healthspan.  However, her love of demanding sports resulted in overtraining syndrome (OTS).

More than 90 years ago, physiologists recognized that sustained, intense training reduces athletic performance by perturbing multiple body systems.

Mary Grace’s arthritic shoulder, painful knees, hips, elbow, neck, back, and feet were the tip of the OTS iceberg. Chronic fatigue, injury proneness, burnout, and brain fog are part and parcel of this sparsely discussed but common condition.[1] 

Adventurous Meets Risk Adverse

For Mary Grace, going under the knife was not worth the risk. As she put it, “I have been in the healthcare business my whole career. No way would I get surgery or joint replacements.” As for giving up on adventure, she stated, “I am too young to grow old.”

Mary Grace knew there was a better option. Her husband, Thomas, accessed his ADRCs for a 25-year-old knee injury with Ambrose’s predecessor group in 2016. He had extensive scar damage from his 1991 orthoscopic surgery. Prior to Ambrose, his doctor recommended a knee replacement and shoulder surgery to repair a torn rotator cuff.

After his ADRC-based protocol, Thomas returned to walking, losing 25 pounds in short order.  Seven years out, Thomas functions fine with his own knee. His shoulder gets a little stiff from time to time, but he works it out with some exercise.

The Autonomic Nervous System – Hanging Fitness in the Balance

The autonomic nervous system (ANS) works without our conscious direction; hence, it is “autonomous.”

The ANS controls inflammation, immune regulation, blood pressure, bladder and bowel function, the gut microbiome, and more. [2]

Working out too hard or for too long imbalances the autonomic nervous system, regardless of how “fit” the person appears. Contrary to popular belief, fitness fanatics get sick more often and are more prone to autoimmune disorders than people in the Blue Zones who garden, walk, and socialize with friends.[3] [4]

A go-go-go life, Covid, Epstein-Barr Virus (mononucleosis), and Lyme Disease infections can have an “overtraining” effect as well.  [5] [6] [7]

Just as Buddha found Nirvana in Nepal, restoring autonomic nervous system (ANS) balance leads to the Nirvana of Health: multisystem balance or homeostasis.

The Autonomic Nervous System Two Divisions.

Sympathetic Division: 

  • Mary Grace thrives on open water swimming in Puerto Vallarta. But when she spotted a hammerhead shark, her sympathetic nervous system went into action. Her blood pressure increased, her heartbeat elevated, and her digestion slowed.

Parasympathetic Division

  • When Mary Grace finishes swimming with the whales, she chills with her husband and friends. Here, the parasympathetic nervous system plays a rest and digest tune. Relaxation and laughter set in. The sympathetic nervous system calms down. [8]

Vagus Nerve

The vagus nerve is our physiology’s fitness coach.  It guides the brain’s connections with the spine, heart, lungs, kidneys, and gut. The VN transitions the autonomic nervous system from stress to rest and back again as appropriate.

When Mary Grace’s sympathetic nervous system was overactivated, her parasympathetic nervous system and vagus nerve underperformed.

A hyperactive sympathetic response raises cortisol and adrenaline levels, lighting the inflammation fire. Then, the immune system throws gas on the flames, resulting in autoimmune diseases. [9]

Parasympathetic underactivity or reduced vagal tone contributes to depression, brain fog, fatigue, insomnia, and weakness. It’s like resting when you don’t want to and not being able to sleep when you need to. [10]

ADRCs Restore ANS Function and Vagal Tone

In 2017, researchers at Houston Methodist documented significant ANS improvements in two patients with autonomic dysfunction (dysautonomia)/ after a single autologous adipose-derived stem cell (ADSC) infusion.

The post-treatment follow-up studies showed:

  • Increased vagal tone
  • Stabilized blood pressure and heart rates
  • Improved circulation in the brain
  • Reduced Inflammatory markers [11]

Mary Grace’s revived mental clarity, energy, and lack of pain indicate her ADRCs restored enduring ANS function.

Tiger’s Travails

In contrast to Mary Grace’s near pain-free turnaround, Tiger Woods epitomizes the risks of excessive training and relying on surgeries, followed by medications, to manage his pain and depression.

  • In 1994, when he was just 18 years old, a surgeon removed two benign tumors and scar tissue from his left knee. Over the next 27 years, he had five back surgeries, four more knee operations, recurrent Achilles tendon tears, and a neck strain.
  • In May 2017, police arrested Tiger on suspicion of driving under the influence. A toxicology report revealed: Two opioids, Vicodin and Dilaudid, a benzodiazepine, Xanax, that induces feelings of calm (anxiolysis), drowsiness, and sleep, Ambien, a “z-drug” for sleep, and a cannabinoid, THC, for pain, according to com.
  • In 2022, a catastrophic car crash nearly killed him, requiring several life-saving surgeries. His doctors operated on him two more times after that. [12]

Ironically, when Mary Grace resumed training for the Appalachian trail, Tiger withdrew from the Hero World Challenge due to plantar fasciitis in November 2022. He was walking too much, a telling sign of how far his fitness had fallen.

At the 2023 Masters, Tiger Woods, in last place, withdrew before play resumed on Sunday due to injury. He told fans this was probably his last attempt at another Green Jacket.

During the same week, Mary Grace described her Appalachian trail training, “I hiked backward and up steep hills. I swam against the tide for a half mile, returned, and swam back against the tide. I bounce back faster. I couldn’t even do that when I was younger.”

While Mary Grace is not a world-class competitive athlete, the comparison holds. Few women have adventured to so many places in so many ways as her.

Mary Grace is just getting started—

And while Tiger continues to suffer, Mary Grace says, “I didn’t realize how much pain I was in until I wasn’t in it anymore.”

Published studies, including over 80 Celution System peer-reviewed papers, support Mary Grace’s conclusion: “After my stem cell treatment, I feel sharper and have better energy. I feel great and am doing more than I have ever done.” [13] [14].[15] [16] [17] [18]

[1] Armstrong LE et al. (2022) Overtraining Syndrome as a Complex Systems Phenomenon. Front. Netw. Physiol. 1:794392.

[2] Bellocchi C et al. The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases. Int J Mol Sci. 2022 Feb 23;23(5):2449.

[3] Kajaia T et al. THE EFFECTS OF NON-FUNCTIONAL OVERREACHING AND OVERTRAINING ON AUTONOMIC NERVOUS SYSTEM FUNCTION IN HIGHLY TRAINED ATHLETES. Georgian Med News. 2017 Mar;(264):97-103.

[4] Leal A et al. ‘Inflammation and Autonomic Function’, Autonomic Nervous System. InTech, Oct. 24, 2018.

[5] Lehmann, M. (1998). Autonomic Imbalance Hypothesis and Overtraining Syndrome. Med. Sci. Sports Exerc. 30 (7), 1140–1145.9

[6] Kreher JB, Schwartz JB. Overtraining Syndrome: A Practical Guide. Sports Health. 2012;4(2):128-138.

[7] Acanfora, D et al. Impaired Vagal Activity in Long-COVID-19 Patients. Viruses 2022, 14, 1035.

[8] Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex–linking immunity and metabolism. Nat Rev Endocrinol. 2012 Dec;8(12):743-54.

[9] Bellocchi C et al. The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases. Int J Mol Sci. 2022 Feb 23;23(5):2449.

[10] Shinba T et al. Major Depressive Disorder and Chronic Fatigue Syndrome Show Characteristic Heart Rate Variability Profiles Reflecting Autonomic Dysregulations: Differentiation by Linear Discriminant Analysis. Sensors (Basel). 2023 Jun 4;23(11):5330.

[11] Numan M et al. Autologous Adipose Stem Cell Therapy for Autonomic Nervous System Dysfunction in Two Young Patients STEM CELLS AND DEVELOPMENT Volume 26, Number 6, 2017

[12] https://bleacherreport.com/articles/2727452-tiger-woods-toxicology-report-reveals-5-drugs-in-his-system-during-dui-arrest  https://www.therecoveryvillage.com/drug-addiction/tiger-woods-dui-prescription-drugs/

[13] Vaquero J, et al. Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury. Cytotherapy. 2017 Jan;19(1):88-94.

[14] Bonsack B, Corey S, Shear A, et al. Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury. CNS Neurosci Ther. 2020;26:603–615.

[15] Mosser DM, Hamidzadeh K, Goncalves R. Macrophages and the maintenance of homeostasis. Cell Mol Immunol. 2021 Mar;18(3):579-587.

[16] Vizoso FJ et al. Mesenchymal Stem Cells in Homeostasis and Systemic Diseases: Hypothesis, Evidences, and Therapeutic Opportunities. Int J Mol Sci. 2019 Jul 31;20(15):3738.

[17] Naik S et al. Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease. Cell. 2018 Nov 1;175(4):908-920. 

[18] Kallal N et al. “Regulation of autoimmune‐mediated neuroinflammation by endothelial cells.” European Journal of Immunology (2024): 2350482.

AMBROSE Cell Therapy

Your Right to Try

Ambrose Cell Therapy Physicians and Facility

Ambrose Cell Therapy Physicians and Facility

Ambrose Cell Therapy Physicians and Facility

Ambrose Cell Therapy, Inc is a management service organization that manages Ambrose Physician Services, PC.

Ambrose Physician Services doctors include:

Dr. Ram Dandillaya, Medical Director, Dr. Ram Dandillaya is the Clinical Chief in the Division of Cardiology at the Cedars-Sinai Medical Center. Dr. Dandillaya clears patients for liposuction unless they choose to do so with their local PCP.

Dr. Nitesh Patel, Attending Physician and Regenerative Injection Specialist, completed a fellowship in interventional pain management at the prestigious Stanford University Medical Center. Dr. Patel requests that patients provide any available recent imaging reports and do a telemedicine consult prior to the procedure.

Dr. Walter Joseph, Plastic Surgeon, completed his residency at the renowned University of Pittsburgh Medical Center. Dr. Joseph requests that patients schedule a telemedicine pre-op with his office.

Dr. Cheryl Jones, Patient Educator, has 25 years of family medicine experience. Her hat is to 1) educate patients so they can make an informed choice and 2) take a brief medical history upon which we will base a preliminary treatment for the patient’s consideration. Dr. Patel finalizes the treatment plan with the patient at the point of care.

Ambrose’s treatments are done at the Illuma Surgery Center, a AAAHC-accredited surgery center in Beverly Hills, CA.

120 Spalding Dr., Suite 205
Beverly Hills, CA 90212
310 975 4586

AMBROSE Cell Therapy

Your Right to Try

What Do Umbilical Cord Stem Cells and Tide Pods Have in Common

What Do Umbilical Cord Stem Cells and Tide Pods Have in Common

What Do Umbilical Cord Stem Cells and Tide Pods Have in Common

“People often ask if stem cells work. Of course, they work. We are all walking stem cell products – the sperm, and the egg,” the revered James Willerson, MD, Ph.D. said in a talk in 2011.[1]

The Tide Pod Teenage Eating Fad, Gronk, and Reverse Psychology
What do dentists, chiropractors, anti-aging doctors, the Four Seasons Maui Spa, and the Tide Pods Eating Fad Have in Common?

In 2018, the Teenagers Eating Tide Pods Fad resulted in 10 deaths and 37 reported poison cases.

Proctor and Gamble, Tide’s manufacturer, went on the offensive to protect kids from poisoning themselves.

They even hired NFL superstar Rob Gronkowski to come from behind in the clutch as he had done to win four Super Bowls with Tom Brady. However, Gronk’s YouTube Tide Pod admonishment resulted in more teens taking the challenge.

Contamination, the FDA, and Reverse Psychology
On December 5, 2019,  the FDA warned Liveyon Labs, Inc. that they were selling unapproved, contaminated umbilical cord stem cell products. At least 300 patients had reported bacterial infections tied to Liveyon’s umbilical cord stem cell products.

One day later, the agency issued a press release informing manufacturers, providers, and the public of Liveyon’s issues and the broader scope of their concerns. The other recipients were RichSource Stem Cells, Inc., Chara Biologics, Inc., and R3 Stem Cell, LLC. In total, FDA issued  350 warning letters to manufacturers, healthcare providers, and clinics.

The result: Increasingly, chiropractors, dentists, naturopaths, integrative doctors, infusion clinics, orthopedists, and so on treat patients with unapproved, potentially contaminated, dead stem cells.

Who Killed the Stem Cells
Sadly, as a chiropractor’s patient with long-Covid and congestive heart failure related, “I tried umbilical cord stem cells. They didn’t work.” There were no live stem cells in the product with which he was treated or other commercially available perinatal vials, studies revealed:

  • Cell viability in the cord blood product was less than reported by the manufacturer, the cells were primarily leukocytes, no stem cells were present…”[2]
  • The aggressive marketing approach currently used by practitioners and clinics regarding various birth tissue products as safe and effective “stem cell therapy” is not supported by the existing scientific literature. [3]
  • CFU-Fs, often referred to as stem cells, were not found within any of the commercial UC (umbilical cord) allograft products analyzed, and clinicians should remain wary of marketing claims stating otherwise. [4]
  • Amniotic fluid has been proposed as an allogenic means for introducing MSCs. This study was unable to confirm that commercial AFPs (amniotic fluid products) contain MSCs. [5]

Risk Appetite
But how does the Tide Pod eating fad relate to the umbilical cord stem cell fad? The Tide Pod teenagers and Umbilical Cord Stem Cell (UBSC) patients share an appetite for risk:

  • The more Proctor and Gamble warned kids of the danger of eating Tide Pods, the faster the fad grows.
  • The more FDA warns providers and patients of perinatal stem cells and their exosomes’ risks, the more the fad is becoming a frenzy too.

A 2016 study identified 351 businesses promoting stem cell treatments. Five years later, the same author, estimated more than four times as many businesses (1,480) sell stem cell treatments, approximately half of which (781) promote umbilical, amniotic, or exosome treatments. [6]

More on risk-taking later. First, what are “perinatal stem cells”?

Perinatal Stem Cells
Perinatal refers to just before or shortly after birth. Thus, perinatal stem cells come from birth tissues or fluids, i.e., umbilical cord blood and tissue, placental blood and tissue, and amniotic tissue and fluid.

That sounds good on the surface, but as explained in The Cell Source Debate, mesenchymal stem cells (MSCs) are rare in birth tissues and fluid. There is more to that part of the story to follow.

Exosomes
Cells release tiny sacs or vesicles called exosomes. Like carrier pigeons, exosomes carry messages to nearby cells.

All cells with DNA – cancer, tissue, immune, blood cells, etc. secrete exosomes.

Mesenchymal stem cells (MSCs) release them too. Despite no reported side-by-side in-human studies, this mechanism has led some researchers and amateur stemcellologists to believe they are more effective than MSCs or ADRCs.

And where a therapeutic dose of MSCs might be 40 -100 million cells, exosome manufacturers claim their vials contain hundreds of millions. A South Florida “stem cell physician” touts one billion exosome vials – without evidence that more is better, much less sterile or safe.

Lab techs must multiply the MSCs or exosomes in culture to obtain a relevant dose.  However, maintaining current Good Manufacturing Practices (cGMP) requires adherence to rigorous standards.

Whodunnit?

Wondery’s ten-episode whodunnit, Bad Batch, illustrates the significant safety risks Liveyon’s slick marketing and non-sterile lab practices delivered to patients. In sum, over 200 patients reported severe adverse events.

Additionally, the CDC published its lab findings in the Journal of the American Medical Association (JAMA) in 2021.

Key Points
Question Were infections in patients who received umbilical cord blood products marketed as stem cell treatment associated with product contamination?

Findings In this case series, 20 patients in 8 states, developed bacterial infections after receiving unapproved products marketed as treatment for conditions including chronic pain and degenerative joint conditions. This national investigation found widespread bacterial contamination of undistributed and distributed products from multiple donors, with whole-genome sequencing indicating a common source.

Meaning The findings from this outbreak underscore that unapproved and unproven stem cell products can expose patients to serious risks without clear benefit, including the possibility of product contamination.

Of unopened, undistributed products sampled for testing, at least 1 of 16 bacterial species contaminated 65% (22 of 34 vials). [7]

Liveyon reincarnations
Yet the warnings failed to stem the umbilical cord stem cell (UBSC) tide nor remove dirty cells:

From an angle not addressed by the FDA, a global review of scientific literature across forty studies revealed that “forever chemicals” from toxic plastics were present in 30,000 umbilical cord blood samples.

Further, citing patient reports of adverse events from a Nebraska exosome clinic, the FDA issued a safety warning to the public.

What the hell is reactive arthritis after a “stem cell” injection?
Promoters of perinatal “stem cell” products claim there is no risk of immune rejection. In other words, they say umbilical cord Wharton’s Jelly does not require human leucocyte antigen (HLA) matching to pair patients and donors, as is done for blood or marrow transplants.

However, a mismatched case report contradicts their false claim.
“A 36-year-old man was injected with Wharton’s jelly for low back pain and within 24 hours developed fevers, chills, polyarthritis, and enthesitis. (Enthesitis is inflammation of the ‘enthesis”, which is where a tendon or ligament attaches to a bone.) Infectious disease work-up was negative. Inflammatory markers were elevated and his HLA-B27 antigen was positive. Initial treatment included methylprednisolone and sulfasalazine. This case highlights the unknown dangers of these allogenic injections and physicians should remain cautious about their use until further study and regulation can ensure patient safety.”[8]

An open penitentiary?
If these products are not FDA-approved and the labs do not comply with cGMP, how do companies get away with selling them? The manufacturers claim their products are for research purposes or ignore FDA regulations because they could care less.

  • Invitrix and Vitti Labs use disclaimers to stay one step ahead of the law.
  • Organicell hides behind the veil of several planned or ongoing phase 1 clinical trials.

Everybody speeds
A doctor wanting to participate in the stem cell wild, wild west asked a lawyer specializing in stem cell regulatory affairs:

Doctor: If I need regulatory approval to treat patients with stem cells, how come so many doctors do it anyway?
Lawyer: “Do you speed?”
Doctor: “All the time.”
Lawyer: “Is it illegal?”
Doctor: “I don’t care.”

Stories like Jury Convicts State Lawmaker of COVID-19 Fraud Scheme at Springfield Health Care Charity and Man falsely claiming to use “Stem Cell Therapy” convicted and sentenced to 202 years don’t seem to make a difference.

Stem Cells and exosomes for the healthy, wealthy
NextHealth at the Four Seasons Maui Resort mixes up the mania, offering Vitti Labs’ potentially contaminated umbilical cord “stem cells” and Organicell’s unapproved exosomes in their spa. They offer Stem Cells + Exosomes + Longevity IV Therapy for $16,000, a savings of $2,299.

Contrary to the FDA’s warning letters, a NextHealth patient coordinator insisted that Vitti’s and Organicell’s products are FDA-approved and that the manufacturers certify all lots are contaminant-free. Where did she get that idea?

From another angle, just because something is illegal doesn’t mean clever marketers partnering with iconic brands like the Four Seasons have consulted a lawyer specializing in FDA compliance. Or have read the literature cited herein.

Stem Cell Distributor expands dental practices
At the other end of the spectrum, New Life, an Invitrix and Organicell distributor, “works closely with clinicians and practitioners to enhance their care offerings…and expand their practices with “natural biologics (emphasis added).” But their research products page and disclaimer tell their customers – dentists, chiropractors, nurses, and doctors – their products are not FDA-approved.

Do Stem Cells Work?
“Of course, they work. We are all walking stem cell products – the sperm, and the egg.” James Willerson, MD, Ph.D. Dr. Willerson went on to publish Buying New Soul (2012). Here he hypothesized that adipose tissue was the best source of adult stem cells.

A growing body of literature supports Willerson’s supposition: A PubMed Central Search returned more than 100,000 publications that discuss adipose-derived stem cells. And over 35 published in-human Celution System studies validate the safety and effectiveness of clinical-grade ADRCs.

In contrast, experimenting on patients in dental offices or at ritzy hotels with potentially contaminated “natural biologics” that contain dead stem cells is a risky pod for patients to swallow.

[1] Perin EC. In Memoriam: James T. Willerson, MD (1939-2020). Tex Heart Inst J. 2020 Aug 1;47(4):242-243.

[2] Fortier LA, Cercone M, Keller LE, Delco ML, Becktell L, Wells KV. Amnion and Umbilical Cord–Derived Products in Sports Medicine: From Basic Science to Clinical Application. The American Journal of Sports Medicine. 2021;49(7):1954-1961

[3]https://legislature.vermont.gov/Documents/2020/WorkGroups/Senate%20Health%20and%20Welfare/Bills/S.252/Written%20Testimony/S.252~Jonathan%20Fenton~Consensus%20Statement%20on%20Aggressive%20Marketing%20of%20Birth%20Tissues%20as%20Stem%20Cell%20Therapies~2-28-2020.pdf

[4] Berger DR, Centeno CJ, Kisiday JD, McIlwraith CW, Steinmetz NJ. Colony Forming Potential and Protein Composition of Commercial Umbilical Cord Allograft Products in Comparison with Autologous Orthobiologics. Am J Sports Med. 2021 Oct;49(12):3404-3413.

[5] Panero AJ, Hirahara AM, Andersen WJ, Rothenberg J, Fierro F. Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison. The American Journal of Sports Medicine. 2019;47(5):1230-1235.

[6] Turner L The American stem cell sell in 2021: U.S. businesses selling unlicensed and unproven stem cell interventions Cell Stem Cell 28, November 4, 2021

[7] Hartnett KP, Powell KM, Rankin D, et al. Investigation of Bacterial Infections Among Patients Treated with Umbilical Cord Blood–Derived Products Marketed as Stem Cell Therapies. JAMA Netw Open.2021;4(10): e2128615.

[8] Madhoun et al. Induction of HLA-B27–Associated Reactive Arthritis After a Wharton’s Jelly “Stem Cell” Injection Am J Phys Med Rehabil 2020;99:e142–e145

AMBROSE Cell Therapy

Your Right to Try

A Golden Era of Cell-Assisted Memory and Vascular Health

A Golden Era of Cell-Assisted Memory and Vascular Health

A Golden Era of Cell-Assisted Memory and Vascular Health

Sam’s Patient Reported Outcome

Sam was a productive dentist, recreational golfer, proud parent, and happy husband. However, in 2013 his wife Flo, a retired physician, began a bold twenty-year battle to reverse his dementia, vascular disease, and pre-diabetes. In April 2020, Sam suffered a stroke and contracted Covid and pneumonia in the hospital. He remained there for two months.

In March 2022, Sam and his wife, Flo, exercised Sam’s Right-to-Try AMBROSE Cell Therapy. Seven months later, he stated, “I am a new man. I have much more energy. My thinking is clearer. I was worried about myself at one time, but not anymore.”

We will return to Sam’s story in a moment; first, some background on the power of blood flow and the risks of ischemia (lack of blood flow).

Sam’s Lifeblood –
Ancient Eastern societies (Phoenicians, Persians, Egyptians, and Hebrews) attached beliefs about blood to the origins of religion. Some Greek savants considered blood the same as the soul or spirit.

Further, the Greeks developed the first scientific considerations about blood. Back in Homer’s time (8th or 9th Century BC), they summarized four concepts that remain valid to day:

a) Blood is essential for life
b) Death is considered final when a lack of blood causes it
c) Clashes in which murder and blood make their appearance are horrible
d) Tribes, nations, and families regard blood as a bond

Finally, the Greeks believed good and virtuous blood characterized a courageous, valiant, and principled person.[1]

Following the Ancients’ theme, Merriam-Webster defines lifeblood as “the seat of vitality.” 

Ischemia – Sam’s life suck
In 1885, Rudolph Virchow coined “ischemia” to characterize the lack of blood flow in an organ or tissue. In plain words, ischemia means blood is not moving through your capillaries, blood vessels, veins, or arteries.

The Po River nourishes Northern Italy’s expansive farms. But 2022’s global heat wave starved Italy’s breadbasket of vital nutrients and harmed the economy,

Similarly, Sam’s blood flow feeds his cells, tissues, and organs, but inflammation-induced ischemia sucked the vitality from Sam’s life.

Sam’s long decline

  • Ten years of smoking
  • Decades-long mercury exposure from practicing dentistry; he retired in 2008
  • He ate the standard American diet (SAD) plus over-indulged in mercury-laden sushi.
  • In 2002, he had surgeries for a torn rotator cuff and a fractured left wrist.
  • In 2013, a noticeable cognitive decline set in. His Montreal Cognitive Assessment or the MoCA Test— had diminished to 16 out of 30, or about half of normal. MoCA is the most sensitive test available for measuring dementia.[2]
  • In 2016, Sam’s doctors diagnosed him with vascular dementia and pre-diabetes.
  • Somewhere along the line, he developed chronic lower back pain.
  • In 2020, he suffered an ischemic stroke and contracted Covid and pneumonia in the hospital, where he remained for an additional two months.

In short, Sam’s diffuse (widespread) vascular, metabolic, and musculoskeletal disease foretold of dementia and the stroke yet to come.[3] [4]

Sam’s history epitomizes the complexity of age-related ill health:

  • Many of the factors associated with heart disease – for instance, high blood pressure, high cholesterol, and smoking are evident in patients with dementia and Alzheimer’s Disease (AD).
  • A common cause of dementia is cerebrovascular disease or damage to the blood vessels in the brain.
  • Elevated mercury levels are a less well-discussed culprit of heart disease and neurodegenerative conditions.
  • The risk of vascular dementia increases with a stroke.

Flo’s Relentless Quest
In 2016, Flo found Dr. Dale Bredesen and the RECODE protocol. For several years Sam responded to RECODE. His MoCA score improved from 16 to 19.

Unfortunately, Sam’s vascular disease caught up with him in early 2020. He had a stroke and contracted Covid and pneumonia in the hospital, requiring a two-month stay. Research has since revealed that the Corona-19 virus attacks the endothelium (inner lining of the blood vessels), adding more risk to Sam’s future. [5]

In 2021, Flo, a retired physician, became concerned that her husband had plateaued. After researching stem cell therapy options, she recommended Ambrose Cell Therapy to Sam in 2022.

Sam’s Disease Progression
Sam’s first sign of ischemia was elevated blood pressure or hypertension (HTN). “His BP became a problem at least ten years ago.”, recalled Flo.

Cardiologists refer to HTN as the silent killer because it leads to heart attacks and strokes.

From 2009 to 2019, the deaths attributable to high BP rose by two-thirds, an astonishing number considering that one in four adults take antihypertensive medications.[6] [7]

  • Every cigarette Sam or anyone smokes causes a temporary rise in blood pressure. And smoking leads to hardening and narrowing of the arteries (atherosclerosis). Thus, a smoker’s blood is more likely to clot, forcing the heart to work harder.
  • Mercury toxicity correlates with hypertension, coronary heart disease, cerebrovascular incidents, and atherosclerosis.
  • Insulin resistance, i.e., pre-diabetes, is associated with low cerebral blood flow (perfusion).
  • Pre-diabetes, a hallmark of metabolic syndrome, links to vascular dementia. [8] [9] [10] [11] [12]

Flo’s Distrust
Flo, a retired physician, lacked confidence in the standard-of-care drugs, e.g., Donepezil (Aricept) and Memantine (Namenda). “I didn’t let the doctors put Sam on those medications. I saw they had short-term benefits but could make things worse with long-term use.”

A British study published in 2004 suggested that Aricept has “disappointingly little overall benefit and is not worth the cost.”

Flo also knew to steer clear of drug combinations, including anti-depressants, anti-psychotics, anti-seizure, and sleep meds (polypharmacy). Neurologists prescribe polypharmacy to patients with neurodegenerative diseases despite its well-documented contribution to the progression and severity of dementia. In other words, drug companies profit, and patients pay the price. [13] [14] [15] [16]

In May 2022, Sam presented to Ambrose with:

  • Vascular dementia
  • Post-stroke left-side imbalance and difficulty swallowing
  • Elevated blood pressure, controlled with medication (Losartan)
  • High cholesterol
  • Pre-diabetes HbA1C 6.3, fasting glucose 106.
  • High inflammatory markers, including homocysteine – 8.4
  • Chronic lower back pain
  • Shoulder arthritis
  • Reclusive and depressed

Harnessing Sam’s Innate Biology
Flo believed in the body’s power to heal itself. That is why she was attracted to the RECODE protocol.

After Sam’s improvement stalled, she took the logical next step of researching stem cell therapy. But Google search results ranked common misinformation high. “Aren’t umbilical cord stem cells (UBSCs) more potent and effective than fat stem cells?” she asked.

Our critical review of Tony Robbin’s Life Force sets the record straight: Researchers have established that ADRCs are the most accessible, abundant, and potent cell population. Contrary to the extant dogma, stem cell depletion does not apply to ADRCs.[17]

Dozens of peer-reviewed studies supported the potential to treat Sam’s combined disabilities in a single outpatient procedure.

Making an informed choice
Flo requested papers supporting potential benefits for Sam’s memory.

  • In 2017 the University of Louisville’s Cardiovascular Innovation Institute demonstrated that intravenous delivery of ADRCs could improve blood vessel health. They predicted “the intravenous delivery of this therapeutic cell population would significantly improve tissue perfusion (the passage of blood), particularly in diseases with diffuse (widely spread) vascular involvement.”[18]
  • A just-published Japanese poster presentation reported remarkable improvements in MOCA scores after IV infusion of adipose-derived–mesenchymal stem cells (ADSCs or Ad-MSC).[19]
  • Another study out of Japan demonstrated, “Treatment with Ad-MSC significantly improved HDL, LDL, and remnant-like particle (RLP) cholesterol levels…These findings suggest that Ad-MSC administration is safe and effective in patients developing arteriosclerosis, thereby providing an attractive tool for anti-aging application.[20]
  • Japanese researchers from Nagoya University concluded in a 2022 review article, Adipose-derived regenerative cells as a promising therapy for cardiovascular diseases: an overview, “Therapeutic angiogenesis (new blood vessel growth) has been developed as a new treatment strategy for such patients.” [21]

 Ischemia – the Tip of the Iceberg
A robust body of literature confirms that ischemia is just the tip of the dementia iceberg. As we have discussed in articles on cell-assisted brain care, aging, and long-Covid recovery, chronic disease involves multisystem dysregulation.

A Golden Era of Self-Cell Repair details the research and discovery path upon which we base Ambrose Cell Therapy’s safety and potential effectiveness.  [22]

Sam’s Personalized Protocol
Per the Ambrose Master Protocol:

  1. Ambrose’s board-certified plastic surgeon harvested 370 ccs of adipose tissue. The Celution™ System processed 310 ccs yielding 68 million ADRCs with 92% viability.
  1. Ambrose’s fellowship-trained interventional pain specialist utilized the remaining 60 ccs to deliver 44 injections of PRP-enriched micro-fat:
  • Para-spinal and para-facet injections -24
  • Right shoulder -13
  • Left wrist – 7

Summary of Benefits
Per Flo, over ten months, Sam went from reclusive, demented, and in chronic back pain to socializing with friends, playing an occasional round of golf, and enjoying his grandchildren.

He helps Flo with chores and preparing dinner and takes the initiative to attend church, meditate, and exercise. He engages in conversation without repeating himself. Flo wants to see his short-term memory improve but acknowledges Sam’s significant quality of life improvement.

Consistent with the studies Ambrose provided to Flo, objective evidence indicates cell therapy lowered Sam’s risk of another catastrophic stroke or a heart attack.

  • His blood pressure normalized -120/80 or better most days – allowing him to discontinue losartan in the first few weeks following Sam’s Ambrose.
  • His metabolic health and systemic inflammation showed remarkable improvement.
    • HbA1C – 6.4 to 5.3
    • Fasting glucose – 106 to 99
    • Homocysteine – 8.4 to 6.0

Sam’s cholesterol remained high until Flo put him on Zetia and a low dose of Crestor. The keto diet raises cholesterol in some and lowers it in others.

Setbacks
To be clear, Sam has had a few setbacks, including a bout of severe constipation. Diet changes resolved that issue.

He also had a flare of debilitating back pain. Notably, his current MRI shows multi-level spinal degeneration and facet arthritis. However, his months of better function, including long walks and restarting golf, lend credence to the Ambrose Cell-Assisted Spine Care Hypothesis.

With rest and conservative physical therapy, Sam said, “My back is better.” He resumed his daily walks a few weeks later.

Sam’s Perspective
“Stem cells are the future. I am a new man. I have much more energy. I am thinking much more clearly. I was worried about myself at one time, but not anymore.”

“It’s going well. I am doing very much better. I am playing golf. We are visiting our son and grandchildren in Hamptons this weekend,” declared Sam.

He had quit golf four years ago and had not visited his family in several years.

Details – Sam’s improving quality of life timeline (edited for brevity and clarity):

  • April: Not repeating questions as often, short-term memory starting to improve. Sam’s masseuse noted he didn’t repeat the same question. And Sam asked about her daughter for the first time. He initiated going to exercise, church, and meditating.
  • His blood pressure normalized. He discontinued losartan.
  • May – Sam surprised Flo with Mother’s Day Flowers and teased her that her boyfriend from high school must have sent them.
  • June – He played golf after quitting four years ago. Flo: “Good news Matt, we played golf – 9 holes, he had fun even though he didn’t play well, but he was able to give me some instructions and vice versa. Beautiful day today. He was fine and willing to go when I brought it up. I was so happy.”
  • Left side imbalance from stroke is no longer evident. “He keeps his balance when walking. Swallowing is better.”, said Flo.
  • Their son, Fred, a prominent healthcare mutual fund manager, acknowledged, “Dad is getting better.”, which is also a first.
  • Sam and Flo had dinner with friends in New York City: “We had a good time. Sam had a good conversation with the others. However, he was not in a good mood. It looks like he got out of the wrong side of the bed. Sam did have these kinds of moments a lot, but recently it is unusual.”
  • July – “I have good news this morning. My brother called Sam for his birthday. He did really good. Usually, he talks a little and hands me the phone, but this time they had a long conversation with laughs and jokes. I haven’t seen this for a long, long time. I think it is really positive progress.”
  • August – Sam spoke for himself rather than deferring to Flo on a one-hour follow-up call. “I am a new man. I have much more energy, much more clear thinking. At one time, I was worried about myself, but not anymore,” he stated.
  • Sam and Flo drove to the Hamptons to see their son and children. Their daughter’s family joined them. “Today, Sun played golf with our son, Fred, and our son-in-law, Jim. He had a good round. This trip was the first time Sam packed his things by himself. He didn’t have much anxiety like before…definitely improved. Jim said, ‘Dad is doing better for sure. Whatever I’m doing is helping him. When he played golf, his back was fine.”, Flo shared after the gathering.
  • “We spent all afternoon (at the US Open) watching Medvedev and Coco play in Ashe Stadium. It was fun to be there and feel the action. Overall, we had fun watching the tennis and excitement.”
  • September – Back to East Hampton for their grandson’s birthday. “Our son was surprised we stayed that long. Sam had fun and mingled with the guests. He didn’t have any issues.”
  • October – Flo reports, “I have some good news. We went to speech therapy. Sometimes I don’t hear him well. The therapist asked him lots of questions. She did not want me to answer for Sam. I was delighted to see his improvement.”
  • December 9 – Last night, Sam had a good conversation with his longtime friend in LA. They chatted with each other, including me. Sam was engaged in the conversation. It made me happy. At first, he didn’t remember it the next day, but after a little hint, he got it and remembered.”
  • From Flo: “Sam’s phone has Face ID. I tried to help him log into Fidelity; of course, it didn’t recognize his face. He said, ‘how could you not recognize my wife’s face? Everything in there is hers!’”

As 2022 came to an end, Flo said, “Matt, I’d like to thank you for your support all year long. It’s been a great year for us.”

[1] John Meletis and Kostas Konstantopoulos The Beliefs, Myths, and Reality Surrounding
the Word Hema (Blood) from Homer to the Present Anemia Volume 2010, Article ID 857657

[2] https://www.mocatest.org/about/

[3] Birdsill AC, Carlsson CM, Willette AA, et al. Low cerebral blood flow is associated with lower memory function in metabolic syndrome. Obesity 2013; 21: 1313–1320

[4] Hoscheidt et al.  Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults Journal of Cerebral Blood Flow & Metabolism 37(6)

[5] Levy et al. Endothelial Injury in COVID-19 and Acute Infections Arterioscler Thromb Vasc Biol. 2021;41:1774–1776

[6] Tsao C et al.  Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association Circulation Vol 145 Issue 8 February 2022

[7] Satoh M et al. Lifetime Risk of Stroke and Coronary Heart Disease Deaths According to Blood Pressure Level Hypertension AHA Volume 73, Issue 1, January 2019; Pages 52-59

[8] Patwa J, Flora SJS. Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies. International Journal of Molecular Sciences. 2020; 21(11):3862.

[9] Siblerud, Robert et al. “A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer’s Disease.” International journal of environmental research and public health vol. 16,24 5152. 17 Dec. 2019,

[10] Genchi, Giuseppe et al. “Mercury Exposure and Heart Diseases.” International journal of environmental research and public health vol. 14,1 74. 12 Jan. 2017

[11] Houston, M.C. (2011), Role of Mercury Toxicity in Hypertension, Cardiovascular Disease, and Stroke. The Journal of Clinical Hypertension, 13: 621-627.

[12] Garfield et al.  HbA1c and brain health across the entire glycaemic spectrum. Diabetes Obes Metab.  2021; 23: 1140– 1149.

[13] Cummings, J, Lee, G, Nahed, P, et al.  Alzheimer’s disease drug development pipeline: 2022. Alzheimer’s Dement.  2022; 8:e12295

[14] Cummings, JL, Goldman, DP, Simmons-Stern, NR, Ponton, E.  The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimer’s Dement.  2022; 18: 469– 477.

[15] The scale and profile of global dementia research funding https://alzimpact.org/research

[16] Park, Hae-Young et al. “The Association between Polypharmacy and Dementia: A Nested Case-Control Study Based on a 12-Year Longitudinal Cohort Database in South Korea.” PloS one vol. 12,1 e0169463. 5 Jan. 2017

[17] Willerson J and Perin E Buying New Soul J Am Coll Cardiol. 2012;60(21):2250-2251

[18] Morris ME et al. Systemically Delivered Adipose Stromal Vascular Fraction Cells Disseminate to Peripheral Artery Walls and Reduce Vasomotor Tone Through a CD11b+Cell-Dependent Mechanism STEM CELLS TRANSLATIONAL MEDICINE 2015;4:369–380

[19] Shigematsu, Kazuo, et al. “Repeated intravenous infusion of autologous adipose‐derived stem cells improves cognitive function.” Alzheimer’s & Dementia 17 (2021): e049907.

[20] Ohta et al. Autologous adipose mesenchymal stem cell administration in arteriosclerosis and potential for anti-aging application: a retrospective cohort study Stem Cell Research & Therapy (2020) 11:538

[21] Nagoya J et al Adipose-derived regenerative cells as a promising therapy for cardiovascular diseases: an overview Med. Sci. 84. 208–215, 2022

[22] Hirose, Yujiro et al. Comparison of trophic factors secreted from human adipose-derived stromal vascular fraction with those from adipose-derived stromal/stem cells in the same individuals Cytotherapy, Volume 20, Issue 4, 589 – 591

AMBROSE Cell Therapy

Your Right to Try

A Golden Era of Cell-Assisted Resilience

A Golden Era of Cell-Assisted Resilience

A Golden Era of Cell-Assisted Resilience

RJ’s Patient-Reported Outcome

Sports-related injuries, including concussions and whiplash, three failed shoulder surgeries, an unsuccessful right knee surgery, etc., retired RJ’s dream of playing Major League Baseball.

In May 2022, he exercised his Right to Try AMBROSE Cell Therapy. Seven months later, he says, “Y’all (AMBROSE) changed my life.”

RJ’s Story
RJ played baseball, football, snowboarding, and golf growing up.

“I had some concussions and whiplash from football and a few car accidents along the way.”

RJ’s shoulder issues started in high school. Initially, his doctor thought it was bicep tendonitis. “I had to take a month off every year. It never felt good.”

One issue led to another. “When I was 17, I blew out my left knee running second base. After that, it would give out a lot.” The MRI showed his femur had lengthened, but it had never bothered RJ before the spill.

RJ’s orthopedic surgeon shaved the femur down and cleaned up the knee. “After the surgery, I did P.T. My knee felt better. I could run but couldn’t walk downhill or stairs.”

Jumping ahead, before his AMBROSE Cell Therapy, RJ complained of left knee pain, clicking, and inability to walk downstairs or a hill. His right knee was symptomatic from compensating. “I could run, but it hurt,” he later said.

Resuming RJ’s story: “I went back to playing baseball. My shoulder gave out after the first couple of days.”

“Nothing showed up on my MRI and X-Ray, but I couldn’t move my arm. I went in for exploratory surgery. The surgeon found my rotator cuff and labrum were shredded.

He repaired it, but then every season, it would give out”, RJ recounted.

Doctors refer to the shoulder joint’s major tendons as the rotator cuff. Rotator cuff tears are common injuries. Advances in surgery have improved rotator cuff repairs. But failure rates remain high.

Here, RJ’s massive rotator cuff tear (MRCT) caused disability and pain. An MRCT precipitates a Spiral of Degeneration beginning with inflammation, abnormal immune response, and lack of blood flow. That leads to programmed cell death (apoptosis), scarring, and degeneration.

Unknown to many people and a key reason shoulder surgeries have such a high failure rate, the muscle around the rotator cuff shrinks, and the body replaces it with fatty tissue.

When the tendon and muscle are finally reattached surgically to the shoulder bone, the weakened muscle can’t handle everyday stresses, and the area can be re-injured.

“I tore my rotator cuff and labrum twice more, each followed by another surgery. Both surgeries failed. In between, I ripped a hamstring, broke some fingers, and fractured my hand while stealing second base,” he said.

Cortisone injections, PRP, and physical therapy failed to bring lasting relief.

In his senior year in college and after the last surgery, his baseball coach discouraged RJ from returning to the team.

Allostatic Load and Anti-resilience.
Sterling and Eyer introduced the concept of allostasis in 1988 as stability through change. From the Greek állos, “other,” “different” + stasis, “standing still.” The researchers were imparting the concept of “remaining stable by being variable.”.

Just as a sailor keeps his boat on an even keel despite choppy waters, the body’s biological systems maintain their equilibrium (homeostasis), despite being put through stress.

In contrast, allostatic Load is “the wear and tear on the body” accumulated from repeated or chronic stress. (Bruce McEwen and Eliot Stellar 1993) Sailing across tall breaking waves over and over can cause irreparable damage.

After RJ’s sports injuries, concussions, surgeries, and competitive stress, his physiologic systems were striking out. He descended from an elite baseball player to being told by his college coach that the disabled list was not a viable option.

By age 23, RJ experienced debilitating symptoms beyond losing his ability to throw with his right arm and run the bases. He stopped bouncing back. In other words, allostatic load set in.

Baseline
RJ’s constellation of wear and tear complaints included:

  • Right shoulder pain, decreased mobility, and left shoulder stiffness.
  • Right elbow stiff, made clicking noises, left elbow stiffness though no pain, no clicking
  • Bilateral arms, decreased reflexes with hammer exam
  • Right knee, sharp pain with walking, early knee fatigue with running, aches in cold weather.
  • Left knee clicking, popping, and stiffness from compensating
  • Challenging to walk downstairs or declines.
  • Lower neck – intermittent numbness and radiation of numbness and tingling into the arm
  • Right upper arm, numbness near upper biceps insertion, constant
  • Right upper arm to fingers (middle & ring fingers), tingling, intermittent nerve pain

More concerning, RJ experienced symptoms of multisystem dysregulation:

  • Vertigo, when looking rapidly with turning his head
  • Daily headaches
  • Sleeping 15 hours per day,
  • Waking up drenched from night sweats
  • Depression
  • An extreme tendency to fall asleep (narcolepsy)
  • Chronic fatigue

In short, allostatic load was ahead 3-2 with the bases loaded in the bottom of the 9th inning. The odds were stacked against RJ Surgeries and drugs had failed him. Though recommended, RJ had the good sense of avoiding pain meds and psychotropic drugs such as Prozac, which could have worsened matters.

Fortunately, RJ had the Right to Try AMBROSE Cell Therapy.

ADRC-assisted Resilience
Based on abundant literature, AMBROSE hypothesized that ADRC-based therapy could unburden allostatic load.[1] [2] [3]  [4] [5] [6] [7]  [8] [9] [10] [11]

Further, preeminent researchers from the Texas Heart Institute, University of Tokyo, Cedar-Sinai, and other respected institutions have published studies that support ADRCs’ potential to treat multiple chronic conditions. [12] [13] [14] [15] [16]

The medical team personalized the AMBROSE Master Protocol to address RJ’s unique health challenges.

  1. Fat Harvesting
    Using minimally traumatic water-assisted liposuction technology (WAL), AMBROSE’s board-certified plastic surgeon harvested 580 ccs (19 oz) of adipose tissue. Post-procedure, RJ reported using only Tylenol for a few days.
  1. Spine and Joint Injections
    AMBROSE relied on published research in addressing the patient’s cervical spine and diseased joints with PRP-enriched micronized fat injections. [17] [18] [19] [20] [21] [22] [23]

AMBROSE’s fellowship-trained interventional pain specialist delivered 61 precise injections under real-time ultrasound guidance into RJs:

  • Inflamed cervical spine (22 injections)
  • Arthritic shoulders and bicep tendons (8 injections),
  • Sore elbows (3 injections)
  • Painful, clicking knees (18 injections).

Results
Seven months out, RJ is playing golf, swinging the baseball bat again, running, walking down declines, lifting weights, and coaching high school football and baseball.

As a result of compensating for his bum shoulder, his right elbow became his biggest problem. “My arm feels really good now- no pain, clicking, or stiffness.” He is throwing the baseball again, though, taking his time to rebuild his deconditioned shoulder muscle.

After his knee surgery, his knees deteriorated. He says, “Running is no problem now; The sharp pain and stiffness are gone. I can walk downstairs and hills again. My friends don’t laugh at me anymore.”

“My neck is much better. I don’t have the numbness and tingling. I don’t get dizzy when I turn it to the side. I haven’t recovered full range of motion yet – but that is getting better too.”, RJ added

  1. ADRC-IV Infusion
    RJ received 129 million Celution™ system processed ADRCs with 92% cell viability through IV infusion.

Published research has established that the ADRC-IV infusion reduces neuroinflammation, improves blood flow, restores autonomic nervous system function, and so on. RJ’s real-world results validate the cited studies. [24] [25] [26]

As an aside, our group’s research revealed the Celution system significantly outperforms the Medikhan, Tissue Genesis Icellator, and other commercially available adipose cell processing systems.[27] [28]

IV Results
In line with the cited publications (and others), RJ started feeling better not long after his AMBROSE treatment.

“I don’t feel depressed like I did before. I am optimistic and have more energy. I don’t wake up drenched with sweat and only need about eight hours of sleep now. I used to sleep from 12:00 am to 2:00 pm and take an hour nap too. Now I coach baseball and football 15 hours a day.”, RJ reported.

He went back to the gym, resumed light weightlifting, and lost 15 lbs. – with no change in diet. RJ added, “I haven’t been in this good of shape for at least two years,”

RJ’s benefits signal a reduction in allostatic load and restoration of multisystem homeostasis.

 

RJ is not alone.
Research studies have established a direct link between increasing allostatic Load and all-cause mortality. Unsurprisingly, studies have also connected heart disease, diabetes, kidney disease, lung disease, and so on with allostatic Load. Thus, beyond RJ’s poor health, he was at high risk of getting worse at a young age. [29]

Today’s environmental, psychological, and lifestyle factors are accelerating the time-to-allostatic Load:

Conclusion
 “The doctors and surgery center team were the best I have had. My future has gone from bleak to bright. I appreciate Matt Feshbach, AMBROSE CEO, for his follow-up and friendship. For me, AMBROSE was a grand slam.”, RJ concluded.

[1] Ghachem, A., Fried, L.P., Legault, V. et al. Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems. Biogerontology 22, 63–79 (2021).

[2] Gross, Alden L et al. “Derivation of a measure of physiological multisystem dysregulation: Results from WHAS and health ABC.” Mechanisms of ageing and development vol. 188 (2020): 111258.

[3] Guidi J, Lucente M, Sonino N, Fava G, A: Allostatic Load and Its Impact on Health: A Systematic Review. Psychother Psychosom 2021;90:11-27.

[4] Hirose Y et al. Comparison of trophic factors secreted from human adipose-derived stromal vascular fraction with those from adipose-derived stromal/stem cells in the same individuals Cytotherapy, 2018; 20: 589–591

[5] VL Negenborn et al. Autologous Fat Grafting as a Last Resort for Unsustainable Pain in a Woman with Multiple Osteochondromas Archives of Plastic Surgery Vol. 44 No. 2 March 2017

[6] S Tamburino et al The Role of Nanofat Grafting in Vulvar Lichen Sclerosus: A Preliminary Report Arch Plast Surg 2016;43:93-95

[7] H Riyat et al Autologous fat grafting for scars, healing and pain: a review Scars, Burns & Healing Volume 3: 1–

[8] T Lopatina et al. (2011) Adipose-Derived Stem Cells Stimulate Regeneration of Peripheral Nerves: BDNF Secreted by These Cells Promotes Nerve Healing and Axon Growth De Novo. PLoS ONE 6(3): e178991

[9] S.  Seigo et al, Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration, Journal of Orthopaedic Science, Volume 18, Issue 1,2013, Pages 145-151

[10] Blaszkiewicz, M., Wood, E., Koizar, S. et al. The involvement of neuroimmune cells in adipose innervation. Mol Med 26, 126 (2020)

[11] F Caviggioli, M.D. Autologous Fat Graft in Postmastectomy Pain Syndrome Plastic and Reconstructive Surgery August 2011

[12] S. Kesten and JK Fraser Autologous Adipose Derived Regenerative Cells: A Platform for Therapeutic Applications Advanced Wound Healing Surgical Technology International XXIX

[13] Nguyen A et al. Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) 69, 170e179

[14] Guo J et al. Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) 69, 180e188

[15] Al-Ghadban S, Artiles M, Bunnell BA. Adipose Stem Cells in Regenerative Medicine: Looking Forward. Front Bioeng Biotechnol. 2022; 9:837464. Published 2022 Jan 13.

[16] J. Willerson and E. Perin Buying New Soul J Am Coll Cardiol. 2012;60(21):2250-2251

[17] Ibrahim, Samir, Rybacka-Mossakowska, Joanna and Michalak, Sławomir. “Fat graft – the natural choice for reconstructive, regenerative and aesthetic surgery” Medical Journal of Cell Biology, vol.5, no.2, 2017, pp.113-117. https://doi.org/10.1515/acb-2017-0008

[18] Heather Vinet-Jones*,1 & Kevin F Darr Clinical use of autologous micro-fragmented fat progressively restores pain and function in shoulder osteoarthritis Regen.Med. (2020) 15(10), 2153–2161

[19] Striano Rd, Malanga G, Bilbool N, Azatullah K. Refractory shoulder pain with osteoarthritis, and rotator cuff tear, treated with micro-fragmented adipose tissue. J. Orthopaedics Spine Sports Med. 2(1), 14–19 (2018).

[20] Lädermann A, Denard PJ, Burkhart SS. Management of failed rotator cuff repair: a systematic review. J ISAKOS. 2016;1(1):32-37. doi:10.1136/jisakos-2015-000027

[21] Heather Vinet-Jones & Kevin F Darr Clinical use of autologous micro-fragmented fat progressively restores pain and function in shoulder osteoarthritis Future Medicine Ltd Regenerative Medicine Volume 15, Issue 10, October 2020, Pages 2153-2161

[22] D.M. Robinson, C. Eng, M. Mitchkash, A.S. Tenforde, J. Borg-Stein Outcomes after Micronized Fat Adipose Transfer for Glenohumeral Joint Arthritis and Rotator Cuff Pathology: a Case Series of 18 Shoulders Muscles, Ligaments and Tendons Journal 2020;10 (3)

[23] Itro, A. et al. Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review. Pharmaceutics 2022, 14, 1151.

[24] J Rosenstein, J Krum & C Ruhrberg VEGF in the nervous system Organogenesis 6:2, 107-114; April/May/June 2010; © 2010 Landes Bioscience

[25] Numan MT et al. Autologous Adipose Stem Cell Therapy for Autonomic Nervous System Dysfunction in Two Young Patients. Stem Cells and Development 2017 26:6, 391-393 

[26] J. Vaquero et al Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury Cytotherapy, 2018; 20: 806–819

[27] A Caplan PhD Mesenchymal Stem Cells J Orthop Res, Vol. 9, No. 5, 1991

[28] Skok M. Mesenchymal stem cells as a potential therapeutic tool to cure cognitive impairment caused by neuroinflammation. World J Stem Cells 2021; 13(8): 1072-1083

[29] P.G. Shiels et al. Circulating markers of ageing and allostatic load: A slow train coming Practical Laboratory Medicine 7 (2017) 49–5451

AMBROSE Cell Therapy

Your Right to Try

A Golden Era of Cell-Assisted Spine Care

A Golden Era of Cell-Assisted Spine Care

A Golden Era of Cell-Assisted Spine Care

In 2016, Barbara suffered from debilitating spinal stenosis. After failing to respond to chiropracty, physical therapy, medication, and steroids, Barb accessed a new option: The stem cells and other regenerative cells residing in her fat or adipose-derived regenerative cells (ADRCs). Five years since her treatment, Barb says that cell therapy “saved my future.”

In 2018, Trish, Jeff, and Kathy lived with complex, debilitating health conditions, including spine-related pain. After they had failed to get relief from conventional and integrative medicine, each chose to exercise their Right to Try AMBROSE Cell Therapy under the Federal Right to Try Act of 2017. Remarkably, over two years post-cell therapy, they all report their spine-related symptoms and dysfunction don’t hold them back anymore. But what is the scientific back story that led to their sustained outcomes? And what was the catalyst for a Golden Era of Spine Care?

 Is Conventional Spine Care Antiquated?
Spine care has its origins in antiquity. The Edwin Smith surgical papyrus, an Egyptian document written in the 17th century BC, is the first known discussion of neck and back-related injuries. Hippocrates (4th century BC) experimented with traction or local pressure to correct spinal deformities. Aristotle also contributed to our current day understanding of the neck and spine.

Few individuals in history have made as many contributions to so many disciplines as Leonardo da Vinci. Included in his vast body of work, Da Vinci sketched the first accurate depiction of the spine. [1]

As a result, knowledge of the neck and back, and their related disorders, have evolved since the Renaissance Man’s illustrations.

Early researchers proposed that neck and back pain resulted from the stress of heavy loads and age-related wear and tear on the discs. Then, in 1978, White and Panjabi published Clinical Biomechanics of the Spine. Here, they connected all the mechanical factors involved in neck and back health.  Technically speaking, they found that in addition to vertebrae, our muscles, tendons, ligaments, blood vessels, and nerves (soft tissues) play significant roles in spine health and disease. White and Panjabi named those pieces of the puzzle the Functional Spine Unit (FSU).

But there was still more to be discovered than the FSU. More recently, researchers began focusing on the vicious interplay involved with traumatic injuries, wear and tear, inflammation, and other diseases (co-morbidities). For example, patients with heart disease, diabetes, neurologic conditions, and autoimmune diseases have a higher prevalence of spine disorders than others without those conditions. In fact, Barb, Trish, Kathy, and Jeff each lived with other chronic debilitating conditions, including arthritis, hypermobility, kidney failure, and spinal cord injury, respectively. [2] [3] [4] [5]

In 2001, Patricia Zuk, Ph.D. et al., working in a UCLA lab, accomplished a (non-obvious) leap forward for patients living with neck and back pain. Zuk’s group discovered mesenchymal stem cells (MSCs) were residing in adipose tissue. But how did their seemingly unrelated research catalyze a Golden Era of Spine care? We will answer that in a moment first; why was a new regenerative option needed in the first place?

 Failed Back Surgery Syndrome
Despite those thousands of years of research and development, more people than ever are suffering from spine-related pain. Besides contributing to the opioid epidemic, the number of spine surgeries increases year in and year out.

Unfortunately, downsides to spine surgery, including high rates of complications, readmissions to the hospital, and poor outcomes, are common. [6] [7] As a result, approximately 4 million individuals live with failed back surgery syndrome (FBSS) in the U.S. Tragically, a spinal fusion gone wrong caused Jeff’s spinal cord injury.

Doctors call those with FBBS and others unwilling to risk a surgical intervention “no-option patients. Jeff’s spinal cord injury resulted from a spine surgery, which upon a second opinion, turned out to be unnecessary in the first place. Barb, Kathy, and Trish opted not to pursue surgery out of concern for those risks.”

 Is there more to spine health than meets the eye?
Circling back, in the early 1500s, Leonardo da Vinci took an unusual interest in tree anatomy. His Rule of Trees explained the balance between the trunk and branches of a tree. He counted the rings in tree trunks to determine “the nature of past seasons.”

Perhaps it wasn’t coincidental that he sketched the spine, tree trunk, and branches, respectively? Let’s look at it this way: The tree’s trunk supports the crown and branches. Likewise, a healthy neck and back do the work of a strong tree.  But even the strongest and thickest tree branch cannot handle a heavy load if the tree’s trunk is weak. Similarly, our legs, arms, hands, and feet can be affected by a degenerated FSU.

Ideally, our spines are a harmony of functional bones and soft tissues. The back and neck rely on all those elements to hold us upright and be mobile. But when the soft tissues atrophy or become arthritic, they pressure nerves, thus contributing to spine-related symptoms.

  • Trish lived with sciatica, numbness, stiffness, and pain.
  • Kathy’s bad neck kept her awake at night.
  • Barbara’s situation prevented her from working, gardening, driving, and pottery.

Most vexing, back-related discomfort doesn’t discriminate: Gardners, crossfitters, weightlifters, golfers, and aging couch potatoes can end up unable to function without pain for varied reasons. [8]

ADRCs – the Spine’s Arborist
An arborist cultivates trees; tree removal is a last resort. The first thing that goes through their minds is how to save the tree. To do their jobs, arborists cultivate the whole tree. They use fertilizer, irrigation, and other regenerative tools to restore the tree’s trunk, limbs, and leaves.

Around 2010, Zuk’s discovery of stem cells in fat came into play when some innovative doctors began treating spine patients with ADRC-based protocols. Their strategy was not dissimilar to an arborist’s. They recognized that a veritable pharmacopeia in a person’s fatty tissue could reduce arthritis and regenerate the supportive soft tissues in the neck and lower back. Back surgeries change the anatomy while cell therapy is, well, therapeutic.

Just as an arborist uses an array of skills to rehabilitate diseased trees, ADRCs use multiple mechanisms of action to rehab the FSU. At least as necessary, ADRCs restore balance or homeostasis in the systems that feed, care for, and defend the spine. In other words, better vascular, immune, metabolic, and nervous system wellness contributes to overall improvements.

In summary, not only did AMBROSE cell therapy help Barb, Jeff, Kathy, and Trish avoid risky surgeries, but all reported being more active, increased energy, and an improved sense of wellbeing.

[1] Bowen G et al Leonardo da Vinci (1452–1519) and his depictions of the human spine
Childs Nerv Syst (2017) 33:2067–2070

[2] M. Shamji et al. Proinflammatory Cytokine Expression Profile in Degenerated and Herniated Human Intervertebral Disc Tissues Arthritis Rheum. 2010 July; 62(7): 1974–1982

[3] J Gallo Inflammation and its resolution and the musculoskeletal system J Orthop Translat. 2017 July; 10: 52–67

[4] Asadian et al. Diabetes Mellitus, a new risk Factor for lumbar spinal stenosis: a Case–Control study. Clinical Medicine Insights: Endocrinology and Diabetes 2016:9 1–5

[5] Lotan R, Oron A, Anekstein Y, Shalmon E, Mirovsky Y. Lumbar stenosis and systemic diseases: is there any relevance? J. Spinal Disord. Tech. 2008;21(4):247-51.

[6] Camino Willhuber et al. Analysis of Postoperative Complications in Spinal Surgery, Hospital Length of Stay, and Unplanned Readmission: Application of Dindo-Clavien Classification to Spine Surgery Global Spine Journal July 2018

[7] Chase D. The opioid crisis is partly fueled by insurers and employers’ approach to back pain. StatNews. statnews.com/2019/03/27/opioid-crisis-insurersemployers- back-pain/. Published March 27, 2019.

[8] J Abbas et al Paraspinal muscles density: a marker for degenerative lumbar spinal stenosis? BMC Musculoskeletal Disorders (2016) 17:422

AMBROSE Cell Therapy

Your Right to Try

Celution™ System Peer-Reviewed Papers

Celution™ System Peer-Reviewed Papers

Celution™ System Peer-Reviewed Papers

Cytori Citations

Akita, S., et al. “Autologous Adipose-Derived Regenerative Cells Are Effective for Chronic Intractable Radiation Injuries.” Radiation Protection Dosimetry, vol. 151, no. 4, 2012, pp. 656–660., https://doi.org/10.1093/rpd/ncs176.

Andjelkov, Katarina, and Zoran Maricic. “Posterior Fourchette Fissure Resolution after Injection of Autologous Adipose-Derived Regenerative Cells.” Obstetrics & Gynecology, vol. 129, no. 3, 2017, pp. 497–499., https://doi.org/10.1097/aog.0000000000001906.

Arkoulis, Nikolaos, et al. “Stem Cell Enriched Dermal Substitutes for the Treatment of Late Burn Contractures in Patients with Major Burns.” Burns, vol. 44, no. 3, 2018, pp. 724–726., https://doi.org/10.1016/j.burns.2017.09.026.

Aronowitz, Joel A., and Joshua D.I. Ellenhorn. “Adipose Stromal Vascular Fraction Isolation: A Head-to-Head Comparison of Four Commercial Cell Separation Systems.” Plastic and Reconstructive Surgery, vol. 132, 2013, p. 48., https://doi.org/10.1097/01.prs.0000435915.06075.66.

C. Calabrese, A. Kothari, S. Badylak, G. Di Taranto, M. Marcasciano, et al. Oncological safety of stromal vascular fraction enriched fat grafting in two-stage breast reconstruction after nipple sparing mastectomy: long-term results of a prospective study Eur Rev Med Pharmacol Sci. 2018 Aug;22(15):4768-4777. doi: 10.26355/eurrev_201808_15610. PMID: 30070312.

Calcagni, Maurizio, et al. “The Novel Treatment of SVF-Enriched Fat Grafting for Painful End-Neuromas of Superficial Radial Nerve.” Microsurgery, vol. 38, no. 3, 2016, pp. 264–269., https://doi.org/10.1002/micr.30122.

Cervelli, Valerio, et al. “Application of Enhanced Stromal Vascular Fraction and Fat Grafting Mixed with PRP in Post-Traumatic Lower Extremity Ulcers.” Stem Cell Research, vol. 6, no. 2, 2011, pp. 103–111., https://doi.org/10.1016/j.scr.2010.11.003.

Choi, Jae Young, et al. “Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study.” Yonsei Medical Journal, vol. 57, no. 5, 2016, p. 1152., https://doi.org/10.3349/ymj.2016.57.5.1152.

Daumas, A., et al. “Long-Term Follow-up after Autologous Adipose-Derived Stromal Vascular Fraction Injection into Fingers in Systemic Sclerosis Patients.” Current Research in Translational Medicine, vol. 65, no. 1, 2017, pp. 40–43., https://doi.org/10.1016/j.retram.2016.10.006.

Foubert, P, et al. “ ADIPOSE-DERIVED REGENERATIVE CELLS PROMOTE PROLIFERATION OF CORNEAL EPITHELIAL CELL AND CORNEAL WOUND HEALING.” Cytori Therapeutics.

Foubert, Philippe, et al. “Autologous Adipose-Derived Regenerative Cell Therapy Modulates Development of Hypertrophic Scarring in a Red Duroc Porcine Model.” Stem Cell Research & Therapy, vol. 8, no. 1, 2017, https://doi.org/10.1186/s13287-017-0704-1.

Foubert, Philippe, et al. “Preclinical Assessment of Safety and Efficacy of Intravenous Delivery of Autologous Adipose-Derived Regenerative Cells (ADRCs) in the Treatment of Severe Thermal Burns Using a Porcine Model.” Burns, vol. 44, no. 6, 2018, pp. 1531–1542., https://doi.org/10.1016/j.burns.2018.05.006.

François, Pauline, et al. “Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods.” Cells, vol. 9, no. 10, 2020, p. 2158., https://doi.org/10.3390/cells9102158.

Fraser, John K., et al. “The Celution®System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.” Advances in Wound Care, vol. 3, no. 1, 2014, pp. 38–45., https://doi.org/10.1089/wound.2012.0408.

Gentile, Pietro, et al. “Breast Reconstruction with Enhanced Stromal Vascular Fraction Fat Grafting.” Plastic and Reconstructive Surgery – Global Open, vol. 3, no. 6, 2015, https://doi.org/10.1097/gox.0000000000000285.

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Gotoh, M, et al. “LONG – TERM DURABILITY OF EFFICACY AND SAFETY OF REGENERATIVE TREATMENT OF MALE STRESS URINARY INCONTINENCE USING AUTOLOGOUS ADIPOSE – DERIVED REGENERATIVE CELLS.” Urology Department, Nagoya University Graduate School of Medicine.

Granel, Brigitte, et al. “Safety, Tolerability and Potential Efficacy of Injection of Autologous Adipose-Derived Stromal Vascular Fraction in the Fingers of Patients with Systemic Sclerosis: An Open-Label Phase I Trial.” Annals of the Rheumatic Diseases, vol. 74, no. 12, 2014, pp. 2175–2182., https://doi.org/10.1136/annrheumdis-2014-205681.

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Guillo, L., Grimaud, F., Houser, F. et al. Three-year outcome of local injection of autologous stromal vascular fraction cells and microfat in refractory perianal fistulas of Crohn’s disease. Stem Cell Res Ther 13, 67 (2022). https://doi.org/10.1186/s13287-022-02738-x

Haahr, Martha Kirstine, et al. “A 12-Month Follow-up after a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial.” Urology, vol. 121, 2018, https://doi.org/10.1016/j.urology.2018.06.018.

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Jørgensen, Mads Gustaf, et al. “Adipose-Derived Regenerative Cells and Lipotransfer in Alleviating Breast Cancer-Related Lymphedema: An Open-Label Phase I Trial with 4 Years of Follow-Up.” Stem Cells Translational Medicine, vol. 10, no. 6, 2021, pp. 844–854., https://doi.org/10.1002/sctm.20-0394.

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Kuzma-Kozakiewicz, Magdalena, et al. “Intraspinal Transplantation of the Adipose Tissue-Derived Regenerative Cells in Amyotrophic Lateral Sclerosis in Accordance with the Current Experts’ Recommendations: Choosing Optimal Monitoring Tools.” Stem Cells International, vol. 2018, 2018, pp. 1–16., https://doi.org/10.1155/2018/4392017.

Lasso, José M., et al. “Injection Laryngoplasty Using Autologous Fat Enriched with Adipose-Derived Regenerative Stem Cells: A Safe Therapeutic Option for the Functional Reconstruction of the Glottal Gap after Unilateral Vocal Fold Paralysis.” Stem Cells International, vol. 2018, 2018, pp. 1–15., https://doi.org/10.1155/2018/8917913.

Lathan, Rashida, et al. “Ischemic and Perfused Kidney Treated with Non-Cultured Adipose-Derived Regenerative Cells Increase the Immune and Regulatory Transcriptome.” Transplantation, vol. 104, no. S3, 2020, https://doi.org/10.1097/01.tp.0000699408.64700.70.

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Shimizu, Shinobu, et al. “Design of a Single-Arm Clinical Trial of Regenerative Therapy by Periurethral Injection of Adipose-Derived Regenerative Cells for Male Stress Urinary Incontinence in Japan: The ADRESU Study Protocol.” BMC Urology, vol. 17, no. 1, 2017, https://doi.org/10.1186/s12894-017-0282-7.

Shimizu, Yuuki, et al. “Adipose-Derived Regenerative Cells for Cardiovascular Regeneration – A Novel Therapy for the Cardiac Conduction System –.” Circulation Journal, vol. 79, no. 12, 2015, pp. 2555–2556., https://doi.org/10.1253/circj.cj-15-1106.

Shimizu, Yuuki, et al. “Rationale and Design of Therapeutic Angiogenesis by Cell Transplantation Using Adipose-Derived Regenerative Cells in Patients with Critical Limb Ischemia ― Tact-ADRC Multicenter Trial ―.” Circulation Reports, vol. 2, no. 9, 2020, pp. 531–535., https://doi.org/10.1253/circrep.cr-20-0055.

Shimizu, Yuuki, et al. “Therapeutic Angiogenesis for Patients with No-Option Critical Limb Ischemia by Adipose-Derived Regenerative Cells: Tact-ADRC Multicenter Trial.” Angiogenesis, vol. 25, no. 4, 2022, pp. 535–546., https://doi.org/10.1007/s10456-022-09844-7.

Shimizu, Yuuki, et al. “Therapeutic Lymphangiogenesis with Implantation of Adipose‐Derived Regenerative Cells.” Journal of the American Heart Association, vol. 1, no. 4, 2012, https://doi.org/10.1161/jaha.112.000877.

Suzuki, Junya, et al. “No Influence on Tumor Growth by Intramuscular Injection of Adipose-Derived Regenerative Cells: Safety Evaluation of Therapeutic Angiogenesis with Cell Therapy.” American Journal of Physiology-Heart and Circulatory Physiology, vol. 320, no. 1, 2021, https://doi.org/10.1152/ajpheart.00564.2020.

Szczepanik, Elzbieta, et al. “Intrathecal Infusion of Autologous Adipose-Derived Regenerative Cells in Autoimmune Refractory Epilepsy: Evaluation of Safety and Efficacy.” Stem Cells International, vol. 2020, 2020, pp. 1–16., https://doi.org/10.1155/2020/7104243.

Tsekouras, Anastasios, et al. “Adipose-Derived Stem Cells for Breast Reconstruction after Breast Surgery – Preliminary Results.” Case Reports in Plastic Surgery and Hand Surgery, vol. 4, no. 1, 2017, pp. 35–41., https://doi.org/10.1080/23320885.2017.1316201.

Tsubosaka, Masanori, et al. “The Influence of Adipose-Derived Stromal Vascular Fraction Cells on the Treatment of Knee Osteoarthritis.” BMC Musculoskeletal Disorders, vol. 21, no. 207, 2020, https://doi.org/10.21203/rs.2.21422/v1.

Yamaguchi, Shukuro, et al. “Adipose-Derived Regenerative Cells as a Promising Therapy for Cardiovascular Diseases: an Overview.” Nagoya J. Med. Sci, vol. 84, 2022, pp. 208–215.

Yoshimura, Kotaro, et al. “Cell-Assisted Lipotransfer for Cosmetic Breast Augmentation: Supportive Use of Adipose-Derived Stem/Stromal Cells.” Aesthetic Plastic Surgery, vol. 44, no. 4, 2020, pp. 1258–1265., https://doi.org/10.1007/s00266-020-01819-7.

Yoshimura, Kotaro. “Cell-Assisted Lipotransfer and Therapeutic Use of Adipose Stem Cells Thereafter.” Aesthetic Plastic Surgery, vol. 44, no. 4, 2020, pp. 1266–1267., https://doi.org/10.1007/s00266-020-01781-4.

Zuk, Patricia A., et al. “Human Adipose Tissue Is a Source of Multipotent Stem Cells.” Molecular Biology of the Cell, vol. 13, no. 12, 2002, pp. 4279–4295., https://doi.org/10.1091/mbc.e02-02-0105.

Akita, Sadanori, et al. “Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury.” Stem Cells International, vol. 2010, 2010, pp. 1–8., doi:10.4061/2010/532704.

Albersen, Maarten, and Trinity J. Bivalacqua. “Regenerative Medicine for Erectile Dysfunction Following Radical Prostatectomy: Are We Ready?” EBioMedicine, vol. 5, 2016, pp. 28–29., doi:10.1016/j.ebiom.2016.02.033.

Ashjian, Peter H., et al. “In Vitro Differentiation of Human Processed Lipoaspirate Cells into Early Neural Progenitors.” Plastic and Reconstructive Surgery, vol. 111, no. 6, 2003, pp. 1922–1931., doi:10.1097/01.prs.0000055043.62589.05.

Borowski, David W., et al. “Adipose Tissue–Derived Regenerative Cell–Enhanced Lipofilling for Treatment of Cryptoglandular Fistulae-in-Ano.” Surgical Innovation, vol. 22, no. 6, 2015, pp. 593–600., doi:10.1177/1553350615572656.

Foubert, Philippe, et al. “Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.” Advances in Wound Care, vol. 5, no. 7, 2016, pp. 288–298., doi:10.1089/wound.2015.0672.

Foubert, Philippe, et al. “Uncultured Adipose-Derived Regenerative Cells (Adrcs) Seeded in Collagen Scaffold Improves Dermal Regeneration, Enhancing Early Vascularization and Structural Organization Following Thermal Burns.” Burns, vol. 41, no. 7, 2015, pp. 1504–1516., doi:10.1016/j.burns.2015.05.004.

Fraser, John K, et al. “Plasticity of Human Adipose Stem Cells toward Endothelial Cells and Cardiomyocytes.” Nature Clinical Practice Cardiovascular Medicine, vol. 3, no. S1, 2006, doi:10.1038/ncpcardio0444.

Fraser, John K., et al. “Fat Tissue: An Underappreciated Source of Stem Cells for Biotechnology.” Trends in Biotechnology, vol. 24, no. 4, 2006, pp. 150–154., doi:10.1016/j.tibtech.2006.01.010.

Ganey, Timothy, et al. “Intervertebral Disc Repair Using Adipose Tissue-Derived Stem and Regenerative Cells.” Spine, vol. 34, no. 21, 2009, pp. 2297–2304., doi:10.1097/brs.0b013e3181a54157.

Gentile, Pietro, et al. “A Comparative Translational Study: The Combined Use of Enhanced Stromal Vascular Fraction and Platelet-Rich Plasma Improves Fat Grafting Maintenance in Breast Reconstruction.” Stem Cells Translational Medicine, vol. 1, no. 4, 2012, pp. 341–351., doi:10.5966/sctm.2011-0065.

Haahr, Martha Kirstine, et al. “Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial.” EBioMedicine, vol. 5, 2016, pp. 204–210., doi:10.1016/j.ebiom.2016.01.024.

Henry, Timothy D., et al. “The Athena Trials: Autologous Adipose-Derived Regenerative Cells for Refractory Chronic Myocardial Ischemia with Left Ventricular Dysfunction.” Catheterization and Cardiovascular Interventions, vol. 89, no. 2, 2016, pp. 169–177., doi:10.1002/ccd.26601.

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AMBROSE Cell Therapy

Your Right to Try

A Golden Era of Cell-Assisted Brain Care Ahead

A Golden Era of Cell-Assisted Brain Care Ahead

A Golden Era of Cell-Assisted Brain Care Ahead

Muhammed Ali’s 1960 Olympic Gold medal started his ascent to being “The Greatest,” but the countless blows to his head – which he welcomed to tire his opponent out – ended in a years-long failed fight to save his brain.

In 2016, Parkinson-related issues took his life, though not before he sought out adult stem cell therapy. Unfortunately, Congress had not yet passed the Federal Right to Try Act of 2017.

What if those who first observed Ali’s slurring, shuffling, and memory struggles had known about the healing factors adipose-derived stem and regenerative cells (ADRCs) secrete?
And what if Ali had the Right to Try to access his ADRCs?

Would he have resumed floating like a butterfly and stinging like a bee? No, but that’s not the point, either.

Ali would have had a fighting chance at a better quality of life. Instead, he faced a decades-long struggle with his Parkinson’s symptoms and the PD drug’s side effects of nausea and tremors, not to mention the other medical conditions with which he lived.

Ali’s descent is a stark example of the risks of brain injuries to our long-term brain health.[1] And these risks are not unique to him or boxing.

Tim’s Win
“I raced in hundreds of powerboat races. Maybe I’m lucky…maybe I’m blessed…maybe I’m genetically superior…or maybe I’m all three, with help from my ADRCs!” says Tim.

In 2000, Tim retired from offshore powerboat racing with four world speed records. He once hit upwards of 180 mph.

Arguably more at risk than Ali, he suffered innumerable head traumas, lost consciousness, and survived a near-death coma on the way to winning his Gold Medals.

In the early 2000s, Tim’s family and friends noticed his hands shaking. In 2008, a neurologist diagnosed him with essential tremors.

Essential tremor is a nervous system (neurological) disorder that causes involuntary and rhythmic shaking. It can affect almost any part of your body, but the trembling occurs most often in your hands — especially when you do simple tasks, such as drinking from a glass, handwriting, or tying shoelaces.

“The cause was a breakdown in the electrical connections in the nervous system due to adverse trauma,” Tim’s neuro explained. He forecasted continued deterioration.

Essential tremors are a suspected risk factor for Parkinson’s disease.[2] And as discussed in detail below, concussions significantly increase the risk of Alzheimer’s, Parkinson’s, ALS, and other neurodegenerative disorders.

Tim’s powerboat racing magnified the risk from contact sports. “It’s been determined that offshore race boat drivers experience more G forces in one race than all the astronauts in the history of NASA have experienced put together. The impact would come up your spine. My head would wobble like a bobble doll,” Tim explained.

“I must have had 1,000 concussions while racing. I probably went unconscious 100 times behind the wheel from the G-forces,” Tim estimated.

Before Tim had the “need for speed,” he played high school and college football. “This was in the days long-before helmet-on-helmet rules, and concussion protocols were in place. I remember getting hit in the head, going to the wrong sideline, and being put right back out on the field”, he recalled.

Tim also tells about his near-catastrophic motorcycle accident when he was a teen: “No helmet, of course…in the hospital for ten days…coma, severe concussion.”

Tim’s Right to Try
In March 2016, Tim accessed his ADRCs offshore with AMBROSE’s prior group. (Okyanos Cell Therapy, Freeport, Bahamas). Almost seven years later, he said, “I should be in much worse shape than I am.”

“My tremors are barely noticeable to other people now. I can eat soup without losing 2/3s of it between the bowl and my mouth. My writing isn’t perfect like I learned in Catholic school growing up, but I can sign checks and write legibly. My memory is fine.”

“The benefit of the stem cells is that it reconnected the wiring,” said Tim.

Tim credits his ADRCs-based cell therapy with other unexpected benefits:

  • “I wore glasses when I raced and before my treatment. Afterward, my vision improved to 20/20. I no longer wear glasses, including readers.” Tim is 63 years young.
  • After all the pounding on my ears and brain from racing and playing the drums in high school, I expected to be deaf by now.” he half-joked. “Instead, my hearing, senses of smell, and taste are better than they were before.”

Remarkably, Tim only recently developed high blood pressure and has no joint or spine issues.

Given Tim’s baseline and absence of other interventions, it would be difficult to attribute his sustained six-year improvement to anything other than his ADRC-based treatment.

Thus, we foresee a Golden Era of Brain Care ahead. More on that in a moment; first, some background.

Background
In the late 1970s, boxing fans observed changes in Muhammed Ali’s speed and speech. Others noted that Ali seemed bored and emotionally detached. The Greatest estimated his opponents hit him in the head 29,000 times – that is like being whacked in the skull day in and day out for 79 years.

And even in fights that he won, Ali took some vicious beatings, especially later in his career. He described the epic third fight with Joe Frazier, in which Ali retained his title after 14 brutal rounds, as “the next thing to death.”

In 1984, three years after retiring from the ring, Ali was diagnosed with Parkinson’s Disease (PD). At that time, doctors did not link the brutal poundings with PD.

Further, TBI research did not associate Ali’s brain damage with chronic traumatic encephalopathy (CTE), the term researchers use to describe a disease of the brain (encephalopathy) caused by repeated head traumas.

Nor did his doctors connect CTE to his frequent bouts of pneumonia, infections, or dementia.

Ali’s descent is a stark example of the risks of brain injuries to our long-term brain health.[3] And these risks are not unique to him or boxing.

CTE is Pervasive
Will Smith’s movie, Concussion brought public awareness to the devastation too many football players face later in life. NFL players are paid big bucks for taking three times the risk of dying from brain disorders than the fans watching them. That risk expands to four times for Alzheimer’s and ALS, respectively.[4]

In 2017, the Journal of the American Medical Association published a study revealing bleak futures for former NFL players. Their median age of death was just 67, and out of the 111 post-mortems, 99% — were diagnosed with CTE.

CTE symptoms vary depending on how advanced or severe it is, but people may experience memory problems, mood disorders, depression, and lapses in judgment.

Brain Trauma – Adding Insult to Injury and Injury to Insult

Brain trauma can be mild or minor, severe, or significant. You don’t have to be an NFL player, a boxer, or race powerboats to increase the probability of Alzheimer’s, Parkinson’s, and other neurologic problems.

After head trauma, some victims recover right away, but many suffer from a constellation of disturbances, including fatigue, poor memory, insomnia, pain, vision, speech, and balance difficulties. [5] [6]

Going the Distance from Brain Science to Brain Care
Ali had another fight separate and apart from his Parkinson’s battle: The chasm between the known factors contributing to neurological conditions and the treatment options available to patients suffering from them.

The gap became apparent in 2006 when Dr. William Langford, the first Chief Science Officer of the Michael J. Fox Foundation, published Parkinson’s Complex: Parkinsonism Is Just the Tip of the Iceberg.[7]

In short, Dr. Langford’s seminal paper stated PD was not limited to the loss of dopamine-producing neurons in the substantia nigra. Instead, Parkinsonism involves multisystem breakdowns. Therefore, he said, “Rather, we must deal with all aspects of the disease if we are to modify its progress in a way that truly enhances the lives of our patients over the long term.

Subsequently, researchers discovered the same interconnected dysregulations after a TBI, stroke, spinal cord injury, Alzheimer’s, etc. Brain diseases don’t pull any punches – they spare no physiologic system.

To solve for this, doctors prescribe patients drugs for each ailment or symptom, e.g., Sinemet for Parkinson’s, Ambien for sleep, steroids for arthritis, opioids for pain, and so forth.

Drug side effects include accelerating the decline in cognitive function.[8]
Dr. Armon Neel Jr. cautions that ten drug classes contribute to dementia progression.

Multisystem dysregulation is a chicken and egg problem. Nearly all patients with brain degeneration live with multiple chronic conditions (co-morbidities).

Tim’s ADRCs – Miracle-Gro For His Brain
Miracle-Gro feeds your garden’s soil with the nutrients it needs to grow healthy roots, stems, petals, and leaves. And just as there are situations in which we fertilize a plant lacking vital nutrients, ADRCs secrete growth factors essential to the health of our aging brains, hearts, muscles, nerves, and so on. [9]  Growth factors (GFs) are a type of cytokine or healing molecule that act on other cells to stimulate growth and function.

One such growth factor group is “Neurotrophic factors (NTFs).” Neuro relating to nerve and trophic, from Ancient Greek trophikós, meaning “of food or nourishment.” In other words, NTFs feed our neurons and nerves with nutrients.

Brain-derived neurotrophic growth (BDNF) stimulates new brain cells, brain cell connections, and nerves. It also repairs the myelin sheathing surrounding the nerves.

It gets better: BDNF is anti-inflammatory and prevents programmed cell death (apoptosis) resulting from an injury or disease. [10] [11] [12] [13] [14]

Many benefits are associated with higher levels of BDNF, including improved mood, productivity, and memory. One 10-year study that tracked BDNF levels in adults found that those with low levels were twice as likely to develop dementia and Alzheimer’s than those with the highest levels.[15]

John Hopkins researchers developed a BDNF-blood test that could have predicted the severity of Ali’s head damage and how he would fare. Their study showed that patients with brain injuries have less than one-third of the BDNF as those with healthy brains.

The most severe TBIs had even lower levels- about 5% of normal. Moreover, patients with high levels of BDNF recovered from their injuries six months later. But symptoms lingered at follow-up in patients with the lowest levels of BDNF.[16]

ADRCs also enrich the brain with vascular endothelial growth factor (VEGF). VEGF restores blood flow and reduces inflammation in withering tissues, blood vessels, and organs. One study found higher levels of VEGF in asymptomatic seniors who died with amyloid plaques compared to symptomatic Alzheimer’s patients.

Notably, ADRCs secrete dozens of other healing factors.[17]

In combination, ADRCs restore multisystem balance or homeostasis – at the cellular, tissue, organ, and multisystem levels.

By the way, big pharma can’t discover a single molecule they can sell millions of copies of per year that can restore physiologic balance. Their drugs suppress the disease’s presumed- but often wrong -causes.

Thus, we believe Ali could have benefited from accessing his ADRCs. The medical literature supports it – and so does Tim’s powerful reversal of his symptoms. If only Ali had the Right to Try. [18] [19] [20] [21] [22] [23]

[1] Ledreux A, Pryhoda MK, Gorgens K, Shelburne K, Gilmore A, Linseman DA, Fleming H, Koza LA, Campbell J, Wolff A, Kelly JP, Margittai M, Davidson BS and Granholm A-C (2020) Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers. Front. Neurosci. 14:761.

[2] Tarakad A, Jankovic J. Essential Tremor and Parkinson’s Disease: Exploring the Relationship. Tremor Other Hyperkinet Mov (N Y). 2019; 8:589. Published 2019 Jan 9.

[3] Ledreux A, Pryhoda MK, Gorgens K, Shelburne K, Gilmore A, Linseman DA, Fleming H, Koza LA, Campbell J, Wolff A, Kelly JP, Margittai M, Davidson BS and Granholm A-C (2020) Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers. Front. Neurosci. 14:761.

[4] Lehman EJ, Hein MJ, Baron SL, Gersic CM. Neurodegenerative causes of death among retired National Football League players. Neurology. 2012 Sept 5 [Epub ahead of print].

[5] R. Jorge et al Major Depression Following Traumatic Brain Injury Arch Gen Psychiatry/Vol 61 Jan 2004

[6] D. Nampiaparampil   Prevalence of Chronic Pain After Traumatic Brain Injury A Systematic Review. JAMA.2008;300(6):711–719.

[7] Langston J W The Parkinson’s Complex: Parkinsonism Is Just the Tip of the Iceberg Annals of Neurology Vol 59 No 4 April 2006

[8] Ishii N et al. Polypharmacy Associated with Cognitive Decline in Newly Diagnosed Parkinson’s Disease: A Cross-Sectional Study Dement Geriatr Cogn Disord Extra 2019; 9:338–343

[9] A Caplan PhD MSCs: The Sentinel and Safe-Guards of Injury J. Cell. Physiol. 231: 1413–1416, 2016.

[10] Razavi, Shahnaz et al. “Neurotrophic Factors and Their Effects in the Treatment of Multiple Sclerosis.” Advanced Biomedical Research 4 (2015): 53. PMC. Web. 28 Sept. 2018.

[11] J. K. Huang et al Myelin Regeneration in Multiple Sclerosis: Targeting. Endogenous Stem Cells., The American Society for Experimental NeuroTherapeutics, Inc. 2011

[12] T Lopatina et al. (2011) Adipose-Derived Stem Cells Stimulate Regeneration of Peripheral Nerves: BDNF Secreted by These Cells Promotes Nerve Healing and Axon Growth De Novo. PLoS ONE 6(3): e178991

[13] S.  Seigo et al, Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration, Journal of Orthopaedic Science, Volume 18, Issue 1,2013, Pages 145-151

[14] Xu et al Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis Journal of Neuroinflammation (2017) 14:156

[15] Jiao SS, Shen LL, Zhu C, et al. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl Psychiatry. 2016;6(10):e907.

[16] FK K. Korley et al Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury JOURNAL OF NEUROTRAUMA 33:215–225 (January 15, 2016)

[17] Hirose, Yujiro et al. Comparison of trophic factors secreted from human adipose-derived stromal vascular fraction with those from adipose-derived stromal/stem cells in the same individuals Cytotherapy, Volume 20, Issue 4, 589 – 591

[18] JK Fraser PhD and S. Kesten MD Autologous Adipose Derived Regenerative Cells: A platform for therapeutic applications Advanced Wound Healing Surgical Technology International XXIX

[19] C. Tate and C Case. Mesenchymal Stromal Cells to Treat Brain Injury. Advanced Topics in Neurological Disorders.

[20] S Dobrowolski and G Lepski. Stem Cells in Traumatic Brain Injury. American Journal of Neuroscience 4 (1): 13-24

[21]CS et al. Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children. Neurosurgery 2011; 68: 588–600

[22] N Tajiri et al. Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats. J Neurosci. 2014 Jan 1;34(1):313-26

[23] Sharma et al Cell therapy attempted as a novel approach for chronic traumatic brain injury – a pilot study SpringerPlus (2015) 4:26

AMBROSE Cell Therapy

Your Right to Try

Can something be done for Covid Long-Haulers?

Can something be done for Covid Long-Haulers?

Can something be done for Covid Long-Haulers?

After living with severe long-Covid symptoms and pre-existing health conditions, Brian exercised his Right to Try AMBROSE Cell Therapy in November 2021. He says AMBROSE has had “a massive effect on my health and quality of life.” Brian adds, nine months out, “I am doing things I couldn’t do a month ago.”

Remarkably, Brian’s many benefits occurred despite ongoing business stress and the difficult loss of two family members.

BackgroundSince December 2019, SARS coronavirus 2 (SARS-CoV-2) has spread like wildfire across the globe.  Unlike the seasonal flu or cold, COVID-19 can attack all body systems and multiple organs.

In response to the virus’ scorched earth capabilities, stem cell researchers worldwide have collaborated to improve outcomes for high-risk Covid patients and long-haulers. [1]

The researchers drew from over 200,000 published papers on Mesenchymal Stem Cells (MSCs). By July 2022, their urgency resulted in 6,400 articles or around 12 daily.

The in-human MSC studies included Covid-induced:

  • Acute respiratory distress syndrome (ARDS) [2]
  • Multisystem inflammatory syndrome in children [3]
  • Multi-organ disease, including sudden cardiac arrest [4]
  • COVID-19 pneumonia in April 2020. [5]

Dr. Pietro Gentile and others focused their research on adipose-derived stem cells (ADSCs) and ADRCs.  [6] [7] [8] [9]

Can ADRCs help Covid Long-Haulers?

Most promising for Brian, his long-Covid symptoms intersected with those from hypermobility, concussions, renal failure, Lyme Disease, and post-chemo side effects.

In response to one or more of these insults, our ADRCs secrete growth factors (GFs) and anti-inflammatory signaling proteins or cytokines essential to our brains, hearts, muscles, nerves, cells, and body health in general.

We share more on GFs and cytokines in Brian’s story that follows.

Ambrose patients Trish, Wouter, Kathy, and other patients with brain fog, fatigue, joint pain, and so on responded to ADRC-based therapy.  Therefore, it made sense for Brian to try AMBROSE Cell Therapy.

Brian’s Story
In December 2020, Brian’s doctor admitted him to the Cedar-Sinai ICU with COVID-19, returning home as a Covid long-hauler after two weeks.

After an introductory call with CEO Matt Feshbach, AMBROSE provided an educational MD consult, overview articles, and peer-reviewed papers supporting the safety and potential effectiveness of the therapy for long-Covid and the other conditions affecting him. Brian said,” (Matt) answered my questions. I had sufficient understanding to move forward.”

Covid Long-Hauler Symptoms
Brian experienced classic long-hauler symptoms: brain fog, chronic fatigue, and emotional volatility. As he summarized, “Most of 2021 was a lost year.”

He started to notice benefits shortly after his AMBROSE treatment. “After about a month, I saw a massive improvement in my mental clarity and energy. Business associates said they noticed the difference too. I didn’t realize how bad the fatigue was until I regained my strength.”

Supporting Brian’s statements, ADRCs release “Neurotrophic factors (NTFs),” Neuro relating to nerve and trophic, from Ancient Greek trophikós, meaning” of food or nourishment.”  NTFs, through multiple mechanisms, reduce neuroinflammation and stimulate the development of new brain cells, brain cell connections, and nerves. [10] [11]

Just as fertilizers keep plants healthy and growing, neurotrophic factors work like Miracle Grow for the brain.

Brian’s restored energy and mental clarity make sense in light of the above.

Vasculitis
Covid left Brian with debilitating inflamed blood vessels and swelling in both legs, or vasculitis, an autoimmune condition. He also complained of constant numbness and tingling in both legs (neuropathy). The right leg was worse than the left.

“My vasculitis and neuropathy went away shortly following the treatment.”

In addition to the NTFs, ADRCs secrete Vascular Endothelial Growth Factor (VEGF). VEGF improves circulation, reduces inflammation, and stimulates the growth of new blood vessels.

Here again, it makes sense that Brian’s swollen blood vessels and nerves calmed down. And an abundance of literature supports Brian’s subjective experience. [12] [13]

And back to Brian’s brain: VEGF reduces neuroinflammation and improves blood flow in the brain. In contrast, neuroinflammation and lack of blood flow in the brain cause chronic fatigue, brain fog, and memory issues. [14] [15]

Pre-Existing Conditions
Brian entered the hospital with a galaxy of pre-existing conditions that had failed to improve with surgeries, drugs, and devices.

Before the pandemic, Brian lived with:

  • Obesity
  • Arthritis in his lower back, shoulders, hips, and knees
  • Asthma
  • Fractured ribs
  • Osteopenia (an early stage of osteoporosis) and
  • A mildly enlarged heart and shortness of breath

In summary, Brian suffered from multisystem dysregulation.

His medications included Prednisone 30-mg daily, Singulair, Symbicort, and Spiriva for Asthma. Ambien for sleep.

Can ADRCs help Covid long-haulers with pre-existing conditions?
In 2016 The California Institute of Regenerative Medicine (CIRM) contributed funding to two review papers that supported ADRC-based treatment for Brian’s chronic illnesses. Further, preeminent researchers from Tulane University and other respected research institutions have continued the growing support for ADRCs’ potential to treat multiple diseases. [16] [17] [18]

Obesity
Brian has struggled with his weight since a young age. “I have probably lost 300 lbs. throughout my life. I tried bariatric surgery in 2007 but gained the weight back.”

“Since my treatment, I have dropped about 50 lbs. and have maintained my weight within a lower range with a less restrictive diet for the first time.”

In 1994, super-sleuth Jeffrey M. Friedman of Rockefeller University established fat as an endocrine organ. In simple terms, he discovered adipose cells secrete hormones that regulate weight gain. His insight explains Brian’s improved metabolism and fat burning following his cell therapy treatment. [19] [20]

Wear, Tear, and Trauma
Brian played football in high school, resulting in some head traumas. He was involved in several major motor vehicle accidents in his early 20s. He went unconscious twice. “They took me to the hospital several times; it was pretty bad.”

Football, basketball, baseball, skiing, and excess weight was not kind to Brian’s joints either.

  • Three right-knee operations failed, leaving both knees painful.
  • He experienced degenerative arthritis in his shoulders.
  • His right and left hips were arthritic as well.

Steroid injections in the affected joints failed to give Brian relief. He tried bone-marrow stem cell injections for his shoulders, but that “didn’t work at all.”

Ambrose’s interventional pain specialist developed a personalized treatment plan based on a Master Protocol. He delivered 22 injections of PRP-enriched micronized fat into Brian’s painful joints.

A month out, his PT said, “Brian’s weight-bearing tolerance and conditioning are improving. He’s doing great.”

Eight months out, Brian shared, “My shoulder, hips, and knees feel good. My back is fine.”

Asthma
Brian developed asthma in his 40s after spending a month in China on business. Before his stem cell treatment, he used three inhalers and took 30 mg of prednisone daily.

Nine months after Brian’s AMBROSE treatment, he says, “I have lowered my daily prednisone dose to 10 mg and occasionally miss taking it without an asthma flare. I significantly reduced my use of inhalers, too.”

Fractured Ribs
An asthma-induced coughing attack fractured four ribs on March 1, 2018. After reviewing Brian’s x-rays, his orthopedist told him he could not repair the ribs. Additionally, Brian had an underlying diagnosis of osteopenia, a condition involving reduced bone mass.

Studies showed that ADRCs stimulate bone healing. [21]

The Ambrose physician injected the fractured ribs. Several months later, Brian reported, “My ribs feel like they healed. That is impressive” To be clear, he still experiences mild discomfort, “but nothing like it was before.”

Mildly Enlarged Heart
A 2018 cardiac workup revealed Brian had a mildly enlarged heart and shortness of breath.
His cardiologist and PT agree the shortness of breath is no longer evident.

The PRECISE cardiac cell therapy study demonstrated significant improvements in endurance, thus supporting Brian’s doctor’s observations. [22] A new cardiac workup is in order.

Multisystem Balance Restored
Brian’s patient-reported outcome demonstrates the potential to restore multisystem homeostasis (balance) by utilizing his ADRCs.

Recommending AMBROSE to Family and Friends
“I have recommended Ambrose to my mother and best friend. It makes sense for them to try it too. Both have arthritic joints, back pain, and other medical issues.”

 

 

[1] Yasamineh et al. Spotlight on therapeutic efficiency of mesenchymal stem cells in viral infections with a focus on COVID-19 Stem Cell Research & Therapy (2022) 13:257
[2] Wick K et al. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS JCI Insight 2021;6(11):e148983
[3] Ross Eckard A, Borow KM, Mack EH, Burke E, Atz AM. Remestemcel-L therapy for
COVID-19-associated multisystem inflammatory syndrome in children. Pediatrics. 2021
[4] Yilmaz R et al. Mesenchymal stem cells treatment in COVID-19 patient with multi-organ involvement Bratisl Med J 2020; 121 (12) 847-852
[5] Zeng et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia Aging & Disease Volume 11 Number 2; 216-228, April 2020
[6] Stromal Vascular Fraction or SVF is the generic term for clinical grade adipose-derived regenerative cells.
[7] Pietro Gentile, Aris Sterodimas. Adipose Stem Cells (ASCs) and Stromal Vascular Fraction (SVF) as a Potential Therapy in Combating (COVID-19)-Disease. Aging and disease. 2020, 11(3): 465-469
[8] Alexander RW. (2020) Overview of COVID-19 Lung Damage Clinical Trial Using Cellular
Stromal Vascular Fraction (cSVF) and Functional Respiratory Imaging (FRI) Analysis of Pulmonary Injury
& Post-Viral (SARS-CoV-2) Adult Respiratory Distress Syndrome (ARDS). Stem Cell Res. 1(1)-1-19.
[9] Sanchez-Guijo F et al. Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study EClinical Medicine 000 (2020) 100454
[10] S. Seigo et al, Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration, Journal of Orthopaedic Science, Volume 18, Issue 1,2013, Pages 145-151
[11] Xu et al Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis Journal of Neuroinflammation (2017) 14:156
[12] Liao L. Mesenchymal stem cell and hematopoietic stem cell transplantation for vasculitis. Vasc Invest Ther 2020; 3:88‐93.
[13] Jahangir S et al. New advanced therapy medicinal products in treatment of autoimmune diseases Editor(s): Nima Rezaei, In Translational Immunology, Translational Autoimmunity, Academic Press, Volume 2, 2022, Pages 319 359,
[14] Skok M. Mesenchymal stem cells as a potential therapeutic tool to cure cognitive impairment caused by neuroinflammation. World J Stem Cells 2021; 13(8): 1072-1083
[15] J Rosenstein, J Krum & C Ruhrberg VEGF in the nervous system Organogenesis 6:2, 107-114; April/May/June 2010; © 2010 Landes Bioscience
[16] Nguyen A et al. Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) 69, 170e179
[17] Guo J et al. Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) 69, 180e188
[18] Al-Ghadban S, Artiles M, Bunnell BA. Adipose Stem Cells in Regenerative Medicine: Looking Forward. Front Bioeng Biotechnol. 2022; 9:837464. Published 2022 Jan 13.
[19] Zhang, Y; Proenca, R; Maffei, M; Barone, M; Leopold, L; Friedman, JM (December 1994). “Positional cloning of the mouse obese gene and its human homologue”. Nature. 1994 (372): 425–432
[20] Zuccarini, M et al Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents. Int. J. Mol. Sci.
2022, 23, 1543.
[21] Saxer F et al. Implantation of Stromal Vascular Fraction Progenitors At Bone Fracture Sites: From A Rat Model To A First-In-Man Study STEM CELLS 2016; 00:00-00
[22] Perin E et al., Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial Am Heart J 2014;168:88-95.e2.

AMBROSE Cell Therapy

Your Right to Try