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 25^th 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 95^th 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 15^th percentile before her treatment. Four months after her treatment, she also reached the 95^th 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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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]}

[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.

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 (8^th or 9^th 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.

2. 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.”

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.”

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