Stem Cell Therapy Health Benefits Part Two by Jeffrey Dach MD

Joe is a 62 year old stock broker with low testosterone, type 2 diabetes, insulin resistance, and metabolic syndrome. His labs show a fasting glucose of 120, a hemoglobin A1C of 6.9 and elevated insulin levels, and a testosterone level of 321. Joe’s health will improve once his testosterone levels have improved with either topical or injectable testosterone. The elevated blood sugar and HbA1C will improve with dietary modification, elimination of sugars and processed carbohydrates from the diet.

This article is Part Two of a series. for Part One , Click Here: Stem Cell Therapy Part One

Another option for Joe is regenerative therapy with umbilical stem cell infusion. These are stem cells derived from umbilical cord cells, also called allogenic mesenchymal stem cells (UC-MSCs) usually obtained from the Wharton’s Jelly in the umbilical cord. A number of my patients have traveled to stem cell clinics outside the US in Antigua, Panama and Mexico for stem cell infusions for various medical conditions. Afterwards, they report on the benefits. They must travel outside the US because umbilical cord stem cell treatments are not FDA-approved in the United States. Although this type of therapy is not mainstream medicine, I predict this will be incorporated into mainstream medicine in the near future. Clinics in Antigua, Panama and Mexico operate under local regulations and promote the stem cells for anti-inflammatory, immunomodulatory, and regenerative properties. The benefits of stem cell therapy arise from the paracrine effects, the secretome or secreted substances released by the stem cells, rather than the stem cells actually engrafting and replacing damaged tissue. There is also a benefit from mitochondrial transfer from the stem cells to damaged cells as discussed below. That said, the preclinical data is impressive and worth reviewing for anyone considering this approach. (20)

Header Image: Stem cell IV administration for Duchenne muscular dystrophy …..Author: Alice Pien, MD Creative Commons Attribution-Share Alike 4.0 International license.

Stem Cell Therapy Improves Fasting Blood Sugar Insulin Sensitivity

For patients like Joe who have early type 2 diabetes, stem cell therapy can help improve insulin resistance, fasting blood sugar and hemoglobin A1C markers.

In Vitro Study of Skeletal Muscle Cells

In 2021 Dr. Kyoung Soo Kim did an in-vitro study using insulin-resistant skeletal muscle cells, a model for the insulin resistance of type 2 diabetes. When insulin resistant muscle cells are treated with umbilical cord stem cell factors, this actually reverses the insulin-resistance in the muscle cells. Dr. Kim found a significant increase in glucose uptake as measured by 2-deoxyglucose assay, restoration of glucose (GLUT4) transporters to the cell membrane which allow glucose uptake, and clear activation of the insulin-sensitizing PI3K/Akt pathway. These changes essentially reversed the insulin-resistant state of the muscle cells. (1)

Diabetic Mouse Stem Cell Study

In 2020 Dr. Guang Chen studied human umbilical cord mesenchymal stem cells (HUC-MSCs) given to obese diabetic mice (db/db). The mice were treated with intramuscular injection of stem cells. The treated mice showed lower fasting blood glucose, reduced insulin resistance, decreased inflammatory cytokines TNF-α and IL-6. Skeletal muscle once again emerged as a key target tissue. (2)

Observational Studies in Diabetics

A few small human observational studies of umbilical stem cell (UC-MSC) infusions in type 2 diabetes patients receiving infusions showed reductions in insulin resistance, reduction in insulin requirement, improved C-peptide levels, and better HbA1c, sometimes lasting for months. (3)

In 2022, Dr. Li Zang did a retrospective observational registry study  of 218 type 2 diabetic (T2DM) patients over 6-month follow-up. 83 patients had 12 months follow up. After infusion of allogeneic umbilical stem cells (UC-MSCs) there was significant reduction in insulin resistance, reduced insulin levels, and HbA1c improved significantly at 6 months and 12 months (p=0.016). Benefits and metabolic improvements were sustained up to 12 months. (4)

Positive Effects on Mitochondrial Function

Mitochondrial dysfunction is now thought to be the main cause of insulin resistance and metabolic syndrome. Dysfunctional, damaged mitochondria generate excess reactive oxygen species (ROS), have impaired fatty acid oxidation, have lower energy (ATP) production. This further worsens the insulin signaling in the type two diabetic, thus creating a vicious cycle of gradually worsening fasting blood sugar and hemoglobin A1c, the two main diabetic markers.

Above Image: Mitochondria Schematic Diagram, Courtesy of Wikimedia Commons Public domain. Typical cross-section of a mitochondrion. Their primary function is to convert the energy potential of nutrients into ATP. Author Mariana Ruiz Villarreal LadyofHats.

Restoring Mitochondrial Function with Stem Cell Therapy

Umbilical cord mesenchymal stem cell infusion (UC-MSCs) helps restore mitochondrial function through two major mechanisms. First, the stem cells secrete powerful bioactive factors called the “secretome”.

More on the Secretome

The secretome of umbilical cord mesenchymal stem cells (UC-MSCs) provides paracrine (cell-to-cell signaling) effects, including the restoration of mitochondrial function.

Major Components of the UC-MSC Secretome fall into two broad fractions:

1) Soluble (secreted) factors (proteins, peptides, and small molecules released directly). These are the Cytokines and chemokines: Approximately 90 cytokines have been identified in UC-MSC secretomes, including pro- and anti-inflammatory cytokines such as IL-6, IL-8, IL-10, TGF-β, and CCL2 (MCP-1). These modulate inflammation, promote cell survival, and reduce apoptosis.

Growth factors: VEGF (vascular endothelial growth factor), HGF (hepatocyte growth factor), FGF-2/bFGF (basic fibroblast growth factor), IGF-1/2 (insulin-like growth factors), PDGF (platelet-derived growth factor), EGF (epidermal growth factor), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and others. These support angiogenesis, cell proliferation, neuroprotection, and tissue repair.

Other soluble bioactive molecules: Anti-apoptotic proteins, neurotrophic factors, and immunomodulatory molecules (e.g., those that upregulate BCL-2/BCL-XL and downregulate BAX/BAK/BAD).

2) Insoluble fraction / Extracellular vesicles (EVs):

Primarily exosomes (small EVs ~30–150 nm) and microvesicles, which carry and transfer cargo to recipient cells. These are enriched with miRNAs (micro RNAs) and other RNAs:

Examples include miR-149, miR-25, and miR-326 (which regulate mitochondrial metabolism and activity), as well as let-7-5p and others involved in anti-apoptotic and anti-oxidative pathways.

Proteins and lipids: Membrane proteins (e.g., CD63, CD81, CD9), heat-shock proteins, and lipids that facilitate intercellular communication, mitochondrial protection, and fusion/fission balance (e.g., via upregulation of mfn1/mfn2 genes).

These components collectively exert paracrine effects that protect and restore mitochondrial function by opposing oxidative stress, preventing mitochondrial-dependent apoptosis, balancing mitochondrial dynamics (fission vs. fusion), transferring regulatory miRNAs to modulate mitochondrial genes, and restoring bioenergetic balance and mitochondrial ATP production.

In the context of UC-MSC infusion for mitochondrial restoration, the secretome acts as the primary mechanism (alongside potential direct cell effects or mitochondrial transfer via tunneling nanotubes or EVs). (19-20)

Back to Dr. Kyoung Soo Kim in-vitro skeletal muscle study:

In a 2021 in vitro study by Dr. Kyoung Soo Kim mentioned above, umbilical stem cells (UC-MSC) were used to reverse insulin-resistance in muscle cells, the C2C12 model. This study showed impressive improvement in mitochondrial biogenesis. Various markers improved such as PGC-1α, the master regulator of mitochondrial renewal, mtTFA, and mitochondrial DNA copy number. It also raised mitochondrial membrane potential, significantly lowered both mitochondrial and cellular ROS, improved fatty acid oxidation, and enhanced the cells’ capacity for ATP synthesis. Note: PGC-1α is Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha, and mtTFA is Mitochondrial Transcription Factor A, also called TFAM. These work together to flip the mitochondrial biogenesis switch back on, exactly what is needed to reverse the mitochondrial dysfunction that drives type 2 diabetes. (1)

Above image: Fig 1. Tunneling Nanotubules Red Arrow and Red Box: Cellular mechanisms of intercellular mitochondrial transfer. Authors: Torralba, Daniel, Francesc Baixauli, and Francisco Sánchez-Madrid. “Mitochondria know no boundaries: mechanisms and functions of intercellular mitochondrial transfer.” Frontiers in cell and developmental biology 4 (2016): 107. CC 4.0

Mitochondrial Transfer through Tunnelling Nanotubules

Secondly, the most remarkable thing is umbilical stem cells (UC-MSCs) can directly transfer healthy mitochondria to damaged cells by way of tunneling nanotubes (see above image).

In a 2015 study by Dr. Hung-Yu Lin, umbilical mesenchymal stem cells donated their functioning mitochondria to recipient cells with defective mitochondria. Mitochondria are transferred from the umbilical stem cells to our own damaged cells via long, thin intercellular connections known as tunneling nanotubes (TNTs), and to a lesser extent, through extracellular vesicles. Once the healthy mitochondria are received, the recipient cells in our body are rejuvenated and regain normal mitochondrial respiration, membrane potential, ATP production, and show reduced oxidative stress. This stimulation of mitochondria biogenesis creates new mitochondria, restores cellular energy metabolism, and improves insulin sensitivity. Taken together, these effects on mitochondria and insulin signaling help explain why some patients report relief from fatigue, better energy and improved glycemic control after stem cell therapy. (19)

Umbilical Cord Stem Cell Infusions: What the Medical Literature Tells Us About Health Benefits

Stem cell therapy may be of benefit for patients with chronic illnesses refractory to conventional medical treatments. Here are a few studies showing benefit in chronic illness:

Congestive Heart Failure

In 2017, Dr. Jorge Bartolucci reported the results of the RIMECARD Trial, a double-blind, placebo-controlled Phase 1/2 randomized study. 30 patients with stable congestive heart failure and reduced ejection fraction received a single intravenous infusion of umbilical cord mesenchymal stem cells (UC-MSCs) or placebo. Safety was excellent. There were no infusion reactions, no immune rejection, and no antibody formation against the infused cells. (5)

Improvement in Ejection Fraction

The UC-MSC group showed a statistically significant 7 per cent improvement in left ventricular ejection fraction (+7% at 12 months versus +1.85% in placebo), improvement in functional class, and improved quality-of-life scores. This remains one of the strongest randomized trials demonstrating cardiac benefit from UC-MSC infusions. (5)

15% Increase in Ejection Fraction

In 2015, Dr. Xia Li et al. [86] infused three dosages of cells (3 × 106–5 × 106) intracoronary to 15 older patients (aged 81–92 years) with chronic total coronary occlusion and found a 15% increase in left ventricular ejection fraction (LVEF) after 24 months, a 21% decrease in infarct area, and a decline of New York Heart Association (NYHA) class III to I.

Li, Xia, et al. “Safety and efficacy of intracoronary human umbilical cord-derived mesenchymal stem cell treatment for very old patients with coronary chronic total occlusion.” Current Pharmaceutical Design 21.11 (2015): 1426-1432.

Above Image: Figure 2. Proposed mechanisms of action of UC-MSCs in therapeutic approaches. Courtesy of Can, Alp, et al. “Umbilical Cord Mesenchymal Stromal Cell Transplantations: A Systemic Analysis of Clinical Trials.” Cytotherapy, vol. 19, no. 12, Dec. 2017, pp. 1351–82,

Meta-Analysis of 93 Studies for 53 Conditions

In 2017, Dr. Alp Can did a systematic review of 93 clinical studies involving more than 2,000 patients treated with UC-MSCs for 53 different conditions.

Neurologic diseases
Chonic Stroke, cerebral infarction
Multiple Sclerosis
Spinal Cord Injury with motor and sensory dysfunctions accompanied by neuropathic pain.
Heresitary Spinocerebral ataxia
Cerebellar Atrophy
Neuromyelitis Optica
Radiation Myelitis
Traumatic Brain Injury
Cerebral Palsy
Autism

Hematologic Diseases
Graft vs. Host Disease
Primary Thrombocytopenia
Aplastic Anemia
Leukemia

Immunologic Diseases
Systemic Lupus Erythematosis (SLE)
Hemorrhagic Cystitis
Ulcerative Colitis
Rheumatoid Arthritis

Liver diseases
cirrhosis (n = 8),
primary biliary cirrhosis (n = 1)
ischemic biliary cirrhosis (n = 1)

Cardiac disease
Ischemic coronary artery diseases
acute myocardial infarction (AMI),
heart failure (HF),

Endocrine diseases
Type 1 and Type 2 Diabetes

Musculoskeletal diseases
Duchenne and Becker muscular dystrophies
Non-Union Bone Fracture
Infected Non-Union Fracture
Osteonecrosis Femoral Head

Pulmonary Disease
Pulmonary Fibrosis
Paraquat Lung Injury

Skin Disease
Drug Induces Stevens Johnson Syndrome
Psoriasis Vulgaris

Dr. Alp Can found virtually every one of the 93 studies reported some degree of clinical or laboratory improvement and there was outstanding safety profile across the board, writing:

…[there were] zero reports of tumor formation, long-term adverse effects, or immune rejection even without HLA matching or immunosuppression. Virtually every study reported some degree of clinical or laboratory improvement, although many were small case series. This large review is frequently cited as early proof that UC-MSCs are feasible and well-tolerated across a wide range of diseases. (6)

Type One Diabetes

In 2016, Dr. Jian Cai evaluated UC-MSCs combined with autologous bone-marrow cells delivered via the pancreatic artery in a pilot randomized controlled trial. Forty-two patients with established type 1 diabetes were randomized to stem-cell transplantation or standard care. After one year, the treated group showed a 105% increase in C-peptide (a marker of insulin production), reduced daily insulin requirements by 29%, and better HbA1c. An eight-year follow-up later showed dramatically lower rates of diabetic complications such as neuropathy, nephropathy, and retinopathy. These results suggest meaningful preservation of beta-cell function and long-term metabolic benefit. (7)

Immune and Inflammatory Disease

In a 2021 study, Dr. Mohamed Mebarki used UC-MSCs as “off-the-shelf” therapy for immune and inflammatory diseases including lupus, multiple sclerosis, rheumatoid arthritis, Crohn’s disease, and graft-versus-host disease. The authors found the umbilical stem cell therapy suppresses an overactive immune system, reduces inflammatory cytokines, and promotes tissue repair. Safety and efficacy was excellent. (8)

In an April 2014, Dr. Tokiko Nagamura-Inoue and Hong He explained why umbilical cord MSCs have such great therapeutic potential. Compared with bone-marrow MSCs, the umbilical cord stem cells (UC-MSCs) are easier to obtain, proliferate faster, show stronger homing to damaged tissues, and exert potent anti-inflammatory and regenerative paracrine effects. This paper laid the groundwork for much of later clinical research, and is widely referenced. (9)

Stem Cell Therapy for C0\/1D

In a 2022 study Dr. Chen Yang examined UC-MSC infusions in 293 C0\/1D-l9 patients through a systematic review and meta-analysis. The treated group had a 40% lower mortality rate, reduced systemic inflammation (lower CRP and IL-6), and improved pulmonary symptoms, with no increase in adverse events. These findings reinforced the role of UC-MSCs in modulating hyper-inflammatory states and acute respiratory distress. (10)

Umbilical Cord Stem Cell Therapy for Chronic Prostate Problems

BPH (benign prostate hypertrophy) and chronic prostate inflammation, prostatitis/chronic pelvic pain syndrome (CP/CPPS) is quite common in the over 60 male population. The urologist will offer mainstream treatments such as antibiotics, alpha-blockers, anti-inflammatory drugs, pelvic floor therapy, etc. and these may fail to provide relief, prompt the patient to seek alternative options such as regenerative therapy with umbilical cord-derived mesenchymal stem cells (UC-MSCs). Such treatments are promoted by clinics in Antigua, Mexico and Panama for their potent anti-inflammatory and immunomodulatory effects.

The concept is this: Why not use young, highly proliferative stem cells to calm chronic inflammation in the prostate? The medical evidence for efficacy is still limited and entirely preclinical. There are no published randomized controlled human trials using unmodified UC-MSCs specifically for chronic prostatitis. This tpe of study may never be forthcoming, since stem cells are natural substances that cannot be patented. Since there is no no patent protection for the drug industry, there is no funding for such expensive studies.  As yet, the we have only one well-designed animal study that shows potential benefits.

The Key 2021 Mouse Study on IL-1β-Primed UC-MSCs

In 2021 Dr. Hanchao Liu, Ani Chi, and Jian Dai studied human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs from Wharton’s jelly) in a mouse model of autoimmune prostatitis (NOD-EAP). This model mimics human non-bacterial chronic prostatitis.

Methods in brief: MSCs were isolated from human umbilical cord Wharton’s jelly. A subset of cells was “primed” (pre-treated) with the inflammatory cytokine IL-1β for 48 hours to enhance their therapeutic potency. Primed or unprimed MSCs were infused intravenously into mice with established CP/CPPS. The outcomes measured were pelvic pain (von Frey filament test), prostate histology/inflammation scores, systemic and local immune cell profiles, cytokine levels, and pain-signaling pathways (CCL2, NF-κB, JNK/MAPK). The key results and potential benefits were pain relief:

1) IL-1β-primed UC-MSCs produced a statistically significant reduction in pelvic hyperalgesia (pain) compared with saline controls or unprimed MSCs.

2) Reduced Prostate Inflammation: Histological inflammation scores in the prostate dropped markedly; proinflammatory cytokines decreased while anti-inflammatory markers rose.

3) Immune Modulation: The treatment decreased infiltration of inflammatory cells and increased regulatory T cells both locally in the prostate and systemically in the spleen, blood, lung.

What is the mechanism of action? The primed stem cells (MSCs) showed preferential accumulation in the spleen where they restored systemic immune balance. This led to downregulation of the master inflammatory controller, NF-κB, and JNK/MAPK pathways in the prostate, reduced CCL2 (a key pain/inflammation mediator), and decreased pain-related markers (CGRP, TRPV1) in dorsal root ganglia. The stem cells did not need to home directly to the prostate in large numbers, as the benefit was from systemic immunomodulation rather than direct stem cell engraftment in the prostate. The authors concluded that IL-1β priming enhances the ability of umbilical cord MSCs to alleviate CP/CPPS symptoms by resetting systemic immunity and breaking the cycle of chronic inflammation and pain. (11)

 

Bottom line: Umbilical cord MSC therapy shows mechanistic promise in animal models for reducing inflammation pain through systemic immune modulation, but it remains highly experimental. (11)

Umbilical Cord Stem Cell Therapy for Sensory Neuropathy:

The Stocking-Glove Pattern in Feet and Hands

One of the many complications of type 2 diabetes is bilateral sensory neuropathy, numbness, tingling, burning pain, and loss of sensation starting in the feet and progressing upward in a classic “stocking-glove” distribution. When conventional therapies are fall short and fail to provide relief, patients may seek alternatives, such as regenerative options. Conventional treatments include medications such as gabapentin, SSRI’s, duloxetine, vitamins such as B12, alpha-lipoic acid, benfotiamine and physical therapy. These may provide only partial relief. Many patients are diabetic while others are idiopathic (the etiology is unknown). An alternative therapy worth considering is intravenous or intramuscular umbilical cord-derived mesenchymal stem cells (UC-MSCs), often from Wharton’s jelly. These allogeneic cells are offered at specialized clinics, including those in Antigua, Mexico and Panama for their anti-inflammatory, neurotrophic, and regenerative properties.

Mechanisms: How UC-MSCs May Help Sensory Neuropathy

Umbilical cord MSCs secrete a rich cocktail of neurotrophic factors (BDNF, GDNF, NGF, VEGF) that support nerve repair. They reduce neuroinflammation, promote angiogenesis (new blood vessel formation to improve nerve nutrition), stimulate remyelination of damaged axons, and enhance axonal regeneration. In animal models of diabetic neuropathy, these effects have translated into improved nerve conduction and reduced hyperalgesia (disrupted sensation).

Note: BDNF= Brain derived neuotrophic factor. This stimulated new brain cell growth.GDNF=Glial derived neurotrphic factor. VEGF= vascular endothelial growth factor.

Sensory Neuropathy: 2024 Systematic Review and Meta-Analysis

The strongest clinical data on sensory neuropathy comes from a 2024 systematic review by Dr. Alizadeh who compiled seven human studies involving 400 patients with diabetic peripheral neuropathy. Two of the trials specifically used umbilical cord-derived mesenchymal stem cells (UCMSCs), while others used bone-marrow mononuclear cells. Most treatments were delivered by intramuscular injection. (12)

Key findings included statistically significant improvements in:

1) Motor nerve conduction velocity (MNCV): weighted mean difference +2.2 m/s
2) Sensory nerve conduction velocity (SNCV): +1.9 m/s
3) Vibration perception threshold (VPT): improved by –2.9 (better sensory function)
4) Toronto Clinical Scoring System (TCSS): reduced by –3.6 points (meaning less severe neuropathy symptoms)

In subgroup analysis, UC-MSCs appeared particularly effective for improving motor nerve conduction velocity, while bone-marrow cells showed slightly greater benefit for sensory parameters. Overall, the authors concluded that stem cell therapy (including UC-MSCs) shows significant promise in improving both objective nerve conduction and clinical sensory symptoms in diabetic peripheral neuropathy (DPN). Safety was excellent, with only minor, transient injection-site pain or swelling reported. (12-13)

Ongoing Clinical Trials

Several randomized controlled trials are currently evaluating human umbilical cord MSCs specifically for moderate-to-severe or refractory diabetic peripheral neuropathy (e.g., NCT07183761 DPN trial using intramuscular hUC-MSC injection). These studies will provide higher-quality data in the coming years.

Stem Cell Therapy for Frailty of Aging

In 2026, Dr. Liem T. Nguyen studied umbilical stem cells for frailty of aging in 147 patients aged 60-85. This included parameters of mitochondrial function ove a 9 month extended follow up after two infusions of stem cells. In 2026, Dr. Liem T. Nguyen writes:

Intravenous infusion of allogeneic UC-MSCs showed no safety concerns and was well tolerated in older adults with frailty. Compared to standard care, UC-MSC therapy was associated with statistically significant and sustained changes in physical function, muscle strength, activity, fatigue, knee pain, and quality of life. The treatment correlated with favourable changes in inflammatory, senescence, and mitochondrial biomarkers….UC-MSC therapy demonstrated efficacy, with statistically significant reductions in systemic IL-6 and TNF-α levels compared with controls…Fatigue scores were consistently lower in the UC-MSC group than in controls, indicating durable alleviation of fatigue…Our findings align with previous trials by Tompkins et al. and Zhu et al.,which reported superior physical performance and favourable immunological profiles following MSC infusion. Consistent with these studies, we observed robust treatment effects in mild-to-moderate frailty…UC-MSC-treated group exhibited statistically significant reductions in plasma levels of IL-6, TNF-α, and IL-10 at both one-month and nine-month follow-up, as well as a statistically significant decrease in IL-1β at one month… The reduction of IL-6, TNF-α, IL-10, and IL-1β suggests the anti-inflammatory and immunomodulatory effects of MSC therapy. (21)

The authors also observed improved mitochondrial function after stem cell infusion, writing:

In this study, we evaluated mitochondrial function in patients following MSC infusion. At six months post-infusion, statistically significant differences were observed in mitochondrial maximal respiration and spare respiratory capacity, two indicators of cellular metabolic health and energy production flexibility. Both parameters were notably higher in the UC-MSC group, suggesting that MSC therapy may enhance mitochondrial function. Studies have demonstrated that exercise-induced improvements in mitochondrial function are associated with enhanced muscle strength, faster gait speed, and improved physical performance in older adults. (21)

Important Caveats

Although there is a growing body of encouraging preclinical and clinical trial data, large long-term human clinical trials of stem cell therapy are relatively lacking. The reason for this is that stem cell therapy is a natural substance, and can not be patented, and therefore of little interest to the drug industry. Because of this, there is no industry funding for larger studies which may never be forthcoming. As is true for most medical procedures, the benefits of stem cell therapy may vary, and the benefits may wane over time, over 6 to 22s months. The potential benefits of stem cell therapy are primarily from paracrine signaling, the secretome, rather than the cells permanently engrafting and becoming new nerves or glandular cells.

Some overseas clinics (e.g., Mediland and others) promote UC-MSC or Wharton’s jelly products for chronic prostatitis and report anecdotal improvements in pain, urinary symptoms, and quality of life. These claims should be viewed with caution, and standard of care with your local urologist should be tried first. As mentioned above, for the type 2 diabetic, dietary modification with low glycemic diet, exercise, and conventional medications such as metformin and berberine should be first line therapy. For sensory neuropathy, the benefits, where seen, appear to be driven by anti-inflammatory and neurotrophic effects rather than wholesale nerve replacement. Standard neuropathy care with glycemic control, foot care, physical therapy, and symptom management remains first line treatment. The reader is advised to discuss risks, benefits, and realistic expectations of stem cell therapy personal physician, your neurologist or endocrinologist before traveling abroad for treatment.

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Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my web site: https://drjeffreydachmd.com/
my personal blog: www.jeffreydachmd.com 

Complete List of References

1) Kim, Kyoung Soo, et al. “Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell.” Diabetes & Metabolism Journal, vol. 45, no. 2, 2021, pp. 260–69, https://doi.org/10.4093/dmj.2019.0191.
Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC8024157/.

2) Chen, Guang, et al. “Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Insulin Resistance via PTEN-Mediated Crosstalk between the PI3K/Akt and Erk/MAPKs Signaling Pathways in the Skeletal Muscles of db/db Mice.” Stem Cell Research & Therapy, vol. 11, no. 401, 16 Sept. 2020, https://doi.org/10.1186/s13287-020-01865-7.
Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC7493876/.

3) Chin, Sze-Piaw, et al. “Umbilical Cord-Derived Mesenchymal Stem Cells Infusion in Type 2 Diabetes Mellitus Patients: A Retrospective Cytopeutics’ Registry Study.” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, vol. 18, 2025, pp. 1643–59.
URL: https://www.dovepress.com/umbilical-cord-derived-mesenchymal-stem-cells-infusion-in-type-2-diabe-peer-reviewed-fulltext-article-DMSO (or DOI: 10.2147/DMSO.S507801; also available via PMC).

4) Zang, Li, et al. “Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stem Cells in Chinese Adults with Type 2 Diabetes: A Single-Center, Double-Blinded, Randomized, Placebo-Controlled Phase II Trial.” Stem Cell Research & Therapy, vol. 13, 2022, article 180.
URL: https://link.springer.com/article/10.1186/s13287-022-02848-6 (or DOI: 10.1186/s13287-022-02848-6).
This phase II trial (n=45 T2DM patients in the UC-MSC arm) reported: HbA1c reduced by 1.31% at 48 weeks (vs. 0.63% in placebo; between-group p=0.0081), with more patients reaching <7.0%; insulin dose/requirements significantly lower (27.78% reduction vs. 15.62% in placebo; daily dose 0.45 vs. 0.57 U/kg/day, p<0.05), and some patients became insulin-free for weeks to months; insulin resistance improved (glucose infusion rate via clamp rose significantly from 3.12 to 4.76 mg/min/kg at 48 weeks, p<0.01 vs. placebo); C-peptide showed transient early increases (AUC at 9–20 weeks) but was not sustainably higher. Effects were sustained through 48-week follow-up.

5) Bartolucci, Jorge, et al. “Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial).” Circulation Research, vol. 121, no. 10, 26 Sept. 2017, pp. 1117–28, https://doi.org/10.1161/CIRCRESAHA.117.310712. Full text: https://www.ahajournals.org/doi/10.1161/circresaha.117.310712.

6) Can, Alp, et al. “Umbilical Cord Mesenchymal Stromal Cell Transplantations: A Systemic Analysis of Clinical Trials.” Cytotherapy, vol. 19, no. 12, Dec. 2017, pp. 1351–82,

7) Cai, Jian, et al. “Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion.” Diabetes Care, vol. 39, no. 1, Jan. 2016, pp. 149–57, https://doi.org/10.2337/dc15-1504. Full text: https://diabetesjournals.org/care/article/39/1/149/31805/Umbilical-Cord-Mesenchymal-Stromal-Cell-With.

8) Mebarki, Mohamed, et al. “Human Umbilical Cord-Derived Mesenchymal Stem/Stromal Cells: A Promising Candidate for the Development of Advanced Therapy Medicinal Products.” Stem Cell Research & Therapy, vol. 12, no. 1, 2021, article 152, https://doi.org/10.1186/s13287-021-02222-y. Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC7907784/.

9) Nagamura-Inoue, Tokiko, and He, Hong. “Umbilical Cord-Derived Mesenchymal Stem Cells: Their Advantages and Potential Clinical Utility.” World Journal of Stem Cells, vol. 6, no. 2, 26 Apr. 2014, pp. 195–202, https://doi.org/10.4252/wjsc.v6.i2.195. Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC3999777/.

10) Yang, Chen, et al. “Efficacy of Umbilical Cord Mesenchymal Stromal Cells for the Treatment of COVID-19: A Systematic Review and Meta-Analysis.” Frontiers in Immunology, 2022, article PMC9467457. Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC9467457/.

11) Liu, Hanchao, et al. “IL-1β-Primed Mesenchymal Stromal Cells Exert Enhanced Therapeutic Effects to Alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through Systemic Immunity.” Stem Cell Research & Therapy, vol. 12, no. 1, 25 Sept. 2021, article 514, https://doi.org/10.1186/s13287-021-02579-0. Full text (open access): https://pmc.ncbi.nlm.nih.gov/articles/PMC8466748/ (validated live link as of May 2026).

12) Alizadeh, Seyed Danial, et al. “Human Studies of the Efficacy and Safety of Stem Cells in the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.” Stem Cell Research & Therapy, vol. 15, no. 442, 19 Nov. 2024, https://doi.org/10.1186/s13287-024-04033-3. Full text: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-024-04033-3 (or PMC11577959).

13) Bojanic, C., et al. “Human Umbilical Cord Derived Mesenchymal Stem Cells in Peripheral Nerve Regeneration.” World Journal of Stem Cells, vol. 12, no. 4, 26 Apr. 2020, pp. 288–302, https://doi.org/10.4252/wjsc.v12.i4.288. Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC7202926/.

14) https://pmc.ncbi.nlm.nih.gov/articles/PMC13123506/
Nguyen, Liem T., et al. “Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell infusion for frailty: a phase 2, single-centre, randomised, open-label controlled trial.” EBioMedicine 127 (2026).

15) Transfer of Mitochondria

https://pmc.ncbi.nlm.nih.gov/articles/PMC11073024/
Velarde, Francesca, et al. “Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact.” Cellular and Molecular Life Sciences 79.3 (2022): 177.

16) https://pubmed.ncbi.nlm.nih.gov/40335384/
Li, Bo, et al. “Targeting mitochondrial transfer as a promising therapeutic strategy.” Trends in molecular medicine: S1471-4914.
Intriguingly, mitochondria can transfer between cells, influencing physiological and pathological processes through intercellular trafficking termed ‘mitochondrial transfer.’ This phenomenon is important in maintaining metabolic homeostasis, enhancing tissue regeneration, exacerbating cancer progression, and facilitating immune modulation, depending on the cell type and microenvironment. Recently, mitochondrial transfer has emerged as a promising therapeutic target for tissue repair and antitumor therapy.

17) https://pmc.ncbi.nlm.nih.gov/articles/PMC12344367/
Patel, Jai Chand, Meenakshi Shukla, and Manish Shukla. “From bench to bedside: translating mesenchymal stem cell therapies through preclinical and clinical evidence.” Frontiers in bioengineering and biotechnology 13 (2025): 1639439.
MSCs primarily function through paracrine signaling—secreting bioactive molecules like vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and exosomes. These factors contribute to tissue repair, promote angiogenesis, and modulate immune responses in damaged or inflamed tissues. Recent studies have identified mitochondrial transfer as a novel therapeutic mechanism, where MSCs donate mitochondria to injured cells, restoring their bioenergetic function. This has
expanded the therapeutic potential of MSCs to include conditions such as acute respiratory distress syndrome (ARDS) and myocardial ischemia. Clinically, MSCs have shown efficacy in diseases like graft-versus-host disease (GVHD), Crohn’s disease, and COVID-19.

18) https://pmc.ncbi.nlm.nih.gov/articles/PMC12505854/
Chen, Huan, et al. “Mesenchymal stromal cell-mediated mitochondrial transfer unveils new frontiers in disease therapy.” Stem Cell Research & Therapy 16.1 (2025): 546.
Mitochondrial transfer is a critical cellular process wherein mitochondria are transferred between cells,
playing a pivotal role in modulating cellular homeostasis and function [16]. This transfer occurs through three
primary mechanisms: tunneling nanotubes TNTs, extracellular vesicles, and direct cell–cell contact.

19) Chetty, Shashank, et al. “Umbilical Cord Mesenchymal Stromal Cells—From Bench to Bedside.” Frontiers in Cell and Developmental Biology, vol. 10, 2022, https://doi.org/10.3389/fcell.2022.1006295.

20) Marzookian, Kimia, et al. “Secretome of Human Umbilical Cord Mesenchymal Stem Cells Exerts Protective Impacts on the Blood-Brain Barrier against Alpha-Synuclein Aggregates Using an In Vitro Model.” bioRxiv, 21 Oct. 2023 (preprint), https://doi.org/10.1101/2023.10.21.562544.

21) Nguyen, Liem T., et al. “Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell infusion for frailty: a phase 2, single-centre, randomised, open-label controlled trial.” EBioMedicine 127 (2026).

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Transfer of Mitochondria

22) https://pmc.ncbi.nlm.nih.gov/articles/PMC11073024/
Velarde, Francesca, et al. “Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact.” Cellular and Molecular Life Sciences 79.3 (2022): 177.

MSCs produce cytokines and growth factors, release extracellular vesicles (EVs) containing a regenerative cocktail of transcription factors, mRNAs, microRNAs, and even mitochondria, thus revitalizing the recipient cells. Among the regenerative properties of MSCs, they can fuse with injured cells, such as cardiac and brain cells…Among the most striking paracrine properties of MSCs is mitochondrial transfer. This transfer of mitochondria to damaged cells has inspired the development of new therapies to treat harmed tissue, especially after heart ischemia [28, 29]…. MSCs are the most tested and used cells for cell therapy. They were first described 30 years ago, with over more than 55,000 publications available today [36]. About 1000 clinical trials are registered for MSCs (ClinicalTrials.gov) with ten studies in phase 4, showing promising results, especially for treating osteoarthritis and heart ischemia [37, 38]. …UC-MSCs are being used in 40 clinical trials to treat 13 neurological conditions, such as autism, amyotrophic lateral sclerosis, ataxia, and cerebral palsy. Twenty-three clinical trials were performed with UC-MSCs to treat immunologic disorders including: systemic lupus erythematosus, hemorrhagic cystitis, HIV infection, rheumatoid arthritis and ulcerative colitis. Caritstem®, produced in 2011 by Medipost in Korea, was the first marketable approved UC-MSCs’ allogeneic product to treat traumatic and degenerative osteoarthritis [52]. The second product to obtain commercial authorization was HeartiCellgram®, made by the Korean company Pharmicell; this product is based on the application of autologous BM-MSCs to treat myocardial infarction [53]…in a phase II/III clinical trial, two injections of UC-derived sEVs have shown to improve clinical outcomes in chronic kidney disease, such as eGFR levels and/or serum creatinine [61]. Currently, clinical trials are evaluating the effects of multiple intravenous infusions of UC blood-derived MSC sEVs in diabetes mellitus (type 1) based on preclinical data on mouse models that showed MSC-derived sEVs to increase the regulatory T cells (Treg) population in the spleen and regenerate pancreatic islets (NCT02138331). Other clinical trials using MSC sEVs are studying the effect of these vesicles on macular degeneration and ischemic stroke [57].

MSCs-derived mitochondria, what makes them special

numerous studies have also shown that MSCs have the ability to replace defective mitochondria and compensate their malfunction through an exchange of cell-to-cell mitochondria, known as mitochondrial transfer between MSCs and target cells [68, 69].

23) https://pubmed.ncbi.nlm.nih.gov/40335384/
Li, Bo, et al. “Targeting mitochondrial transfer as a promising therapeutic strategy.” Trends in molecular medicine: S1471-4914.
Intriguingly, mitochondria can transfer between cells, influencing physiological and pathological processes through intercellular trafficking termed ‘mitochondrial transfer.’ This phenomenon is important in maintaining metabolic homeostasis, enhancing tissue regeneration, exacerbating cancer progression, and facilitating immune modulation, depending on the cell type and microenvironment. Recently, mitochondrial transfer has emerged as a promising therapeutic target for tissue repair and antitumor therapy.

24) https://pmc.ncbi.nlm.nih.gov/articles/PMC12344367/
Patel, Jai Chand, Meenakshi Shukla, and Manish Shukla. “From bench to bedside: translating mesenchymal stem cell therapies through preclinical and clinical evidence.” Frontiers in bioengineering and biotechnology 13 (2025): 1639439.
MSCs primarily function through paracrine signaling—secreting bioactive molecules like vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and exosomes. These factors contribute to tissue repair, promote angiogenesis, and modulate immune responses in damaged or inflamed tissues. Recent studies have identified mitochondrial transfer as a novel therapeutic mechanism, where MSCs donate mitochondria to injured cells, restoring their bioenergetic function. This has
expanded the therapeutic potential of MSCs to include conditions such as acute respiratory distress syndrome (ARDS) and myocardial ischemia. Clinically, MSCs have shown efficacy in diseases like graft-versus-host disease (GVHD), Crohn’s disease, and COVID-19.

25) https://pmc.ncbi.nlm.nih.gov/articles/PMC12505854/
Chen, Huan, et al. “Mesenchymal stromal cell-mediated mitochondrial transfer unveils new frontiers in disease therapy.” Stem Cell Research & Therapy 16.1 (2025): 546.
Mitochondrial transfer is a critical cellular process wherein mitochondria are transferred between cells,
playing a pivotal role in modulating cellular homeostasis and function [16]. This transfer occurs through three
primary mechanisms: tunneling nanotubes TNTs, extracellular vesicles, and direct cell–cell contact.

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Published on June 9th, 2026 by Jeffrey Dach MD