Spinal Cord Injury Cell Therapy Hypothesis
Background: In December 2018, AMBROSE Cell Therapy pioneered a novel protocol for Jeff, a patient living with a spinal cord injury. Jeff’s 14-month patient-reported outcome chronicled significant improvements in symptoms, function, and quality of life.
In December 2017, Jeff’s spine surgery gone wrong resulted in an SCI and paraplegia. His extended hospitalization led to an abscessed colon requiring an ileostomy. Compounding matters, he lived with T2 diabetes.
Jeff complained of neck and back pain, neuropathy, scar pain from the ileostomy, claw toes, spasticity, poor balance, diabetes T2, shoulder immobility, and erectile dysfunction (ED). He took seven meds to manage his symptoms, including opioids.
Our in-depth review of published SCI stem cell therapy studies yielded positive results. Thus, AMBROSE curated the literature and developed a personalized protocol for Jeff.
The treatment strategy was unconventional. Rather than only targeting the spinal cord lesion, the AMBROSE medical team addressed Jeff’s array of complaints in a single procedure using a Master Protocol.
In essence, AMBROSE designed one overarching protocol to treat multiple issues in a single treatment including the injury site, using adipose-derived regenerative cells (ADRCs). Our treatment team then personalizes it for each patient.
Importantly, our previous group’s prior successes using a Master Protocol with over 300 patients living with diverse chronic conditions supported our hypothesis. (Okyanos Cell Therapy, Bahamas 2014- 2017).
- A subsequent meta-analysis, Transplantation of mesenchymal stem cells for spinal cord injury: a systematic review and network meta‑analysis, validated the safety and effectiveness of MSC-based treatments for SCI. 
- Researchers had published successful case reports using injections of micronized adipose tissue to address SCI-related musculoskeletal conditions, scar pain, and neuropathy.  
- Published trials for other chronic conditions informed. 
- Urology KOLs advised on a sacral-plexus injection sub-protocol to target bladder and bowel dysfunction.
A wide gap exists between the known pathophysiology of spinal cord injury and the standard of care being relied upon to treat it. Specifically, the damage to the cord incites multisystem dysregulation, including immune, endothelial, metabolic, mitochondrial, and autonomic dysfunction.   
Hence, patients suffer from an array of secondary complications.
Further, the overwhelming insult suppresses spinal cord regeneration, limiting functional recovery. Thus, the expected window of improvement for SCI patients is ~12 months.
As an example, Jeff’s symptoms included 24/7 scar pain, neuropathy, bilateral spasticity, bowel and bladder issues, ED, and impaired balance. At 11 months post-injury, Jeff and his physiatrist recognized his progress had leveled off.
Yet, drug discovery focuses on a single mechanism of action to repair the injury site or suppress a symptom. Put differently, the pharma model of one drug, gene, or cell type to treat a disease has made little progress in improving the prognosis for patients living with spinal cord injuries. This approach neglects a deep body of literature documenting the multiple factors and resulting comorbidities that combine to handicap patients like Jeff.
Multiple Mechanisms of ADRCs
In contrast, ADRCs have multiple mechanisms of action (MOAs) targeting all the factors involved in a chronic condition, including multisystem dysregulation. 
ADRCs home to sites of inflammation and secrete hundreds of bioactive molecules that are anti-inflammatory, immuno-modulatory, angiogenic, anti-apoptotic, and wound healing.
ADRCs work through cell-to-cell communication or the paracrine effect.
In Jeff’s recovery, the restoration of multisystem homeostasis included improved balance, pain scores, bladder, and bowel function, as well as a significant reduction in spasticity. The net result was an elimination of all drugs, engaging in hardcore gym workouts, a return to racing, learning to fly helicopters and scuba diving, plus playing golf three times a week. Though not cured or asymptomatic, Jeff is real-world evidence that ADRCs extended Jeff’s recovery window.
In sum, our preliminary evidence indicates that ADRCs can extend or restart the neurologic window of recovery by restoring multisystem homeostasis.
Why Adipose Tissue?
Unlike other tissue sources of adult stem cells, e.g., bone marrow, ADRCs remain accessible, abundant, and potent throughout one’s life.  Following liposuction, the Celution™ Cell Processing System (Lorem Cytori, Inc.) centrifuges the lipoaspirate and prepares the ADRCs.
Adipose-Derived Regenerative Cells (ADRCs) are the designation for a clinical-grade preparation of stromal vascular fraction (SVF), a heterogeneous population of cells residing on the outer lining of the capillaries in adipose tissue. The cell mix includes MSCs, endothelial cells (ECs), endothelial progenitor cells (EPCs), fibroblasts, T-regulatory cells (Tregs), macrophages, and other immune cells (leukocytes).
ADRCs secrete significantly higher amounts of trophic factors compared to Adipose-Derived MSCs (ADSCs). Therefore, the ADRC secretome amplifies the MOAs of ADSCs, including but not limited to:
- Anti-inflammation and Immuno-modulation,
- Support of growth,
- Differentiation of local stem cells and progenitor cells,
- Anti-scarring, and
Human studies show ADRCs:
- Release factors that down-regulate inflammatory-autoimmune markers, including but not limited to TNF-A, TH17, IL6, and IL2, as well as upregulate IL10.
- Promote the switch from inflammatory macrophages (M1s) to anti-inflammatory macrophages (M2s) via Prostaglandin E2 (PGE2) and the MSCs in the mix.
- Reduce Endothelin-1 (ET-1), a known constrictor of blood vessels, implicated in spinal cord-blood-barrier disruption after the injury.
- Assist in the growth and stabilization of new blood vessels by secreting placental Growth Factor (PGF), Stromal-Derived Factor-1 (SDF-1), and Vascular Endothelial Growth Factor (VEGF).
Notably, a close relationship exists between revascularization and improved functional outcomes after SCI. First, a well-vascularized lesion provides a permissive microenvironment for local tissue survival and nerve regeneration. Improved capillary blood flow, angiogenesis, and B-SC-B integrity facilitate functional recovery. 
ADRCs deliver neurotrophic factors (NTFs) to the CNS, PNS, and ANS. Just as fertilizers keep plants healthy and growing, NTFs stimulate the development of new brain cells, brain cell connections, and nerves.
One such trophic factor is the brain-derived neurotrophic factor or BDNF.
- Repairs the myelin sheathing surrounding the nerves
- Reduces inflammation and,
- Prevents apoptosis that results from an injury or disease.     
Since 2007, no ADRC-related adverse events have been reported.
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 Lorem Cytori, Inc Unpublished internal data