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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.

As of July 2024, Ambrose physicians provide cell therapy services at the Revive Surgery Center, a AAAHC-accredited facility in Pasadena, CA.

333 South Arroyo Parkway, 3rd floor
Pasadena, CA 91105
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.”

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