Stem Cell Research: Reversing Aging

• Cell Type Used: Umbilical Cord Derived Mesenchymal Stem Cells (UMC119-06-05)
• What They Are:
• The Source: Mesenchymal stem cells collected from the umbilical cords of healthy, unrelated donors after full-term births.
• The Goal: This therapy aims to see if an infusion of young, healthy stem cells can improve frailty by reducing inflammation and supporting natural repair mechanisms.
• Delivery Method:
• IV Infusion: The stem cells are administered directly into the bloodstream through an intravenous line.
• The Control: The trial has two parts:
  • Phase I: Simple safety study. All participants receive the stem cell therapy.
  • Phase II: Randomized, single blind, placebo-controlled study. Participants are randomly assigned to receive either stem cells or placebo. Patients don’t know which they received.
• Cell Dosage: Each patient in the treatment group receives one IV infusion containing 100 million cells.
• Schedule: One-time, single IV infusion.

Follow up Schedule

• Patients are monitored for safety for up to 12 months after treatment.
• Effectiveness is measured at several points: approximately 3, 6 and 12 months after infusion.

What They’re Measuring

• Safety: Tracking all side effects during the first year post infusion.
• Health Monitoring: Continuous monitoring of vital signs, bloodwork, physical exams and heart function (ECG).

Other Outcomes (Phase II)

• Frailty Status: Measuring changes in the standard CHS frailty score.
• Physical Function: Assessing improvements in hand grip strength and the “Five Times Sit-to-Stand” test.
• Body Composition: Using DXA scans to measure changes in muscle mass and bone density.
• Quality of Life: Using the SF 12 questionnaire to evaluate improvements in patients’ daily living and overall well-being.

• Cell Type Used: HeXell-2020 — Umbilical Cord-Derived Mesenchymal Stem Cells.
• What They Are:
• The Source: Mesenchymal stem cells are isolated from Wharton’s jelly, the tissue inside umbilical cords of healthy, unrelated donors.
• The Goal: This therapy aims to treat frailty using the anti-inflammatory, regenerative and anti aging properties of young, healthy stem cells.
• Delivery Method:
• IV Infusion: The stem cells are delivered directly into the bloodstream via intravenous infusion.
• The Control: This is an open-label, single arm study. All participants receive stem cells, with no placebo control.
• Cell Dosage: Each infusion contains 50 million cells.
• Schedule:
• Cohort 1: 3 doses given once every two weeks.
• Cohort 2: 6 doses given once every two weeks.

Follow-up Schedule

• Patients will be followed for one year.
• Safety and effectiveness are measured at baseline and then at Weeks 6, 12, 24, 36 and 52.

What They’re Measuring

• Primary Goal (Safety):
• Finding the Right Dose: Identify the Maximum Feasible Dose by monitoring for any serious side effects (Dose-Limiting Toxicities).
• General Safety: Record all side effects and adverse events for up to one year after treatment begins.
• Other Outcomes (Effectiveness):
• Physical Function: Track changes in walking endurance (6-minute walk test), grip strength and overall physical performance (Short Physical Performance Battery).
• Frailty Status: Evaluate changes in the patient’s Clinical Frailty Scale score.
• Quality of Life: Use patient questionnaires, FES-I (fear of falling), PROMIS and SF 36 to assess improvements in physical and mental health.

• Cell Type & Source: The study used allogeneic human umbilical cord derived mesenchymal stem cells. These cells were sourced from the umbilical cords of healthy, full-term donors, not the patients themselves.
• Method: Each patient received two IV infusions, administered 30 days apart.
• Dose: 1 million cells per kilogram of the patient’s body weight for each infusion.
• Passage Number: The stem cells were expanded in a lab, using cells from the fifth passage for infusions.
• Cell Preparation & Quality:
• The cells were manufactured under strict GMP (Good Manufacturing Practice) standards.
• Each batch was verified with specific surface markers (CD73, CD90, CD105) to confirm identity and function.
• Over 90% of the cells were confirmed alive, viable, and free from contamination.

• Safety:
• The treatment was found to be very safe.
• No serious side effects were observed in any patient.
• Minor effects (like temporary dizziness in one patient) were rare and similar to the placebo group.
• Effectiveness:
• Quality of Life: Patients in the stem cell group showed a significant improvement in overall physical quality of life compared to the placebo group, starting just one week after the first infusion and lasting six months.
• Physical Function: Stem cell recipients showed major gains in:
• Grip strength (especially at the 6-month mark)
• Mobility and balance, as measured by the “Timed Up and Go” test
• Walking speed
• Reduced Inflammation: Blood tests revealed significant reductions in TNF-α and IL-17, key inflammatory markers, in the stem cell group by the study’s end.
• How the Cells Worked:
• Calming Chronic Inflammation: The drop in inflammatory markers like TNF-α shows the cells’ strong anti-inflammatory and immune regulating effects.
• Sending Out Healing Signals (Paracrine Effect): The cells likely released beneficial growth factors that helped repair tissue and promote regeneration throughout the body.

• No Control Group in Previous Studies: This trial had a placebo control, but prior frailty studies often did not, making these results stronger and more reliable.
• Small Patient Group: With only 15 patients receiving stem cells, the findings are promising but need confirmation in larger studies.
• Short Follow-Up: The follow-up period was only six months. Future studies need longer tracking to see how long the benefits last.

• The review did not state its objectives as specific questions, but the overall goal was to provide a comprehensive overview of the field. The key implied questions were:
• What are the most promising new therapies for rejuvenating aging skin?
• How do these different treatments work to reduce wrinkles, improve elasticity & restore a youthful appearance?
• What are the current limitations and challenges that are preventing these therapies from being widely used?

• 1. How Stem Cells Are Used for Anti-Aging
• Mesenchymal Stem Cells (MSCs): Explored for reducing wrinkles and improving skin elasticity because they release substances that boost collagen production.
• Adipose-Derived Stem Cells (ADSCs): Taken from fat tissue, these can be injected into the face to restore lost volume and improve texture.
• 2. “Cell-Free” Therapies Are Gaining Traction
• Platelet-Rich Plasma (PRP): Studies suggest PRP can improve fine lines and texture by promoting cellular repair through natural growth factors.
• Exosomes: Tiny vesicles released by cells that may safely accelerate regeneration and reduce inflammation while stimulating collagen.
• Growth Factors & Dermal Fillers: Growth factors stimulate collagen and reduce fine lines; fillers restore lost volume and smooth wrinkles.
• 3. Futuristic Approaches Are on the Horizon
• Gene Editing: Tools like CRISPR are being studied to repair age-related genetic damage in skin cells.
• 3D Bioprinting: Used to develop engineered skin substitutes for cosmetic applications.
• 4. Significant Hurdles Remain
• Safety and Standardization: Long-term safety and consistent preparation methods are lacking, leading to variability and risks.
• Cost and Accessibility: High costs and specialized equipment limit access.
• Ethical Concerns: Stem cell and gene-editing use raises ethical considerations.

• The authors conclude that while regenerative therapies hold great promise for skin rejuvenation, most are still in early experimental or clinical stages.
• For these treatments to become mainstream, the field needs continued research, standardized protocols, and large-scale clinical trials.
• The ultimate goal is to make advanced anti-aging therapies more effective, affordable, and accessible for everyone.

• This review set out to answer some of the biggest questions in the field of anti-aging medicine:
• What does the human evidence really say about using stem cells to treat frailty and rejuvenate skin?
• How do these therapies actually work in the body?
• And what are the real safety risks we need to be aware of?

• 1. Real Improvements in Aging Frailty
• The review looked closely at a series of human trials on a therapy called Lomecel-B for elderly patients experiencing frailty.
• What they found was that a single IV infusion of these stem cells helped elderly patients walk farther and with more ease, improved their overall physical function, and lowered inflammation in their bodies.
• 2. Visible Results in Skin Rejuvenation
• The review highlighted three human studies that showed noticeable cosmetic benefits:
• In one study, injections of a patient’s own fat-derived stem cells (ADSCs) smoothed wrinkles and reduced drooping by an average of 33–40% over a year.
• Another study found that combining microneedling with the liquid from umbilical cord stem cells (their “conditioned media”) made a big difference in skin brightness and texture, more so than microneedling alone.
• A third trial showed that using either microneedling or a laser to deliver the beneficial substances (the “secretome”) from fat-derived stem cells worked well to reduce wrinkles and other signs of sun damage.
• 3. How Stem Cells Seem to Fight Aging
• Repairing Tissue: They can directly replace old or damaged cells by turning into new ones.
• Sending Helpful Signals: They release a mixture of beneficial substances (like growth factors and exosomes) that tell other cells to repair themselves and reduce inflammation.
• Calming Inflammation: They help regulate the body’s inflammatory response, which is a major driver of the aging process.
• 4. Safety Is a Major Concern
• The good news is that in the controlled clinical trials for frailty, no serious side effects were reported.
• However, the review gives a strong warning about the dangers of uncontrolled or unverified therapies.
• It brings up two real-world examples of what can go wrong:
• One case where a patient developed a tumor from a poorly prepared iPSC therapy.
• Another where a patient developed lesions in their spine after receiving stem cells from an unknown, unregulated source.

• The researchers’ final takeaway is that stem cell therapy is a very promising path for fighting aging, but the science needs to be done right.
• They emphasize that before these treatments can be offered to the public, we need large, well-designed clinical trials that follow patients for 5 to 10 years to confirm the long-term benefits and safety.
• Getting the manufacturing process and quality control standardized is the key to making these therapies both safe and effective for everyone.

• What do the results from recent human clinical trials show for treating physical frailty with stem cells?
• What do the results from recent human clinical trials show for rejuvenating aging facial skin?
• What are the key limitations and safety concerns of the current research?
• Why are these two conditions (frailty and skin aging) the main focus of anti-aging stem cell research?

• 1. Effectiveness for Physical Frailty
• Promising Results: The leading therapy being studied is Lomecel-B, made from bone marrow stem cells of young, healthy donors. A key Phase II study found the treatment was well tolerated and modestly but significantly increased the 6-minute walk distance in frail, elderly participants. The best results came from the 100-million-cell dose.
• Reduced Inflammation: The Lomecel-B treatment also significantly reduced blood levels of TNF-alpha, a key chemical marker of chronic inflammation linked to aging.
• 2. Effectiveness for Facial Skin Aging
• Visible Improvements: The main approach uses a patient’s own fat-derived stem cells, often in a preparation called Stromal Vascular Fraction (SVF).
• Positive Results: A key randomized controlled trial found that adding SVF to a standard fat graft significantly improved facial volume, smoothed wrinkles and skin texture, and increased the graft’s survival rate compared to a fat graft alone.
• 3. Limitations and Safety Concerns
• Lack of Standardization: The review found that current trials for aging frailty use different diagnostic tools and outcome measures, making cross-study comparisons difficult.
• Dosing Questions: For the Lomecel-B frailty trial, the best results came from a medium dose, not the highest. The author notes this is “difficult to explain” and highlights the need for more dose-finding research.
• Safety Risk of IV Infusion: A major concern for IV infusions is that animal studies show most stem cells get trapped in the lungs, which could pose safety risks that must be carefully monitored in humans.

• The author concludes that clinical research into stem cells for normal aging is a very new field but has gotten off to a strong start, with numerous trials already launched worldwide.
• The positive results from early- and mid-stage trials for both physical frailty and skin aging are very encouraging.
• The author is hopeful that these efforts will lead to the first approved stem cell anti-aging product in the near future.