This week, we witnessed a remarkable milestone in stem cell therapy. A single infusion of a stem cell-based treatment may have effectively cured 10 out of 12 people with a severe form of type 1 diabetes. One year later, these 10 patients no longer needed insulin to maintain stable blood glucose levels, and their tests showed no evidence of the disease.
In the United States, around 2 million people live with type 1 diabetes, typically diagnosed in childhood. This serious autoimmune condition is caused by the immune system attacking and destroying pancreatic islet cells—specifically, beta cells that produce insulin. Without insulin, glucose cannot enter cells, requiring patients to inject the hormone daily.
People with type 1 diabetes must monitor their blood glucose levels 24/7. High blood sugar can damage the heart, kidneys, eyes, and nerves. If levels drop too low, patients can experience shakiness, fainting, seizures, or even death.
The Breakthrough: Zimislecel
The experimental treatment, called Zimislecel, involves pancreatic islet cells generated in vitro from embryonic stem cells (ESCs). These lab-grown islet cells were infused through the portal vein, traveled to the pancreas, and became established there. Developed by Vertex Pharmaceuticals (Boston), the therapy is undergoing Phase III trials, with FDA approval targeted for 2026.
This pioneering work—conducted by Vertex in collaboration with Harvard researchers—was presented at the American Diabetes Association’s annual meeting and published in The New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2506549 . In this phase 1-2 study, 12 patients received either a single dose of 0.8 billion cells or a double dose of 0.4 billion cells. All were also treated with immunosuppressive therapy. The function of the new islet cells was tracked by measuring serum C-peptide levels.
All 12 patients showed successful engraftment of the transplanted islet cells. None experienced hypoglycemic events, and all maintained hemoglobin A1C levels below 7%, indicating reversal of key diabetic symptoms. Notably, 10 out of 12 became insulin-independent within 12 months—an extraordinary result that could have justified FDA halting a placebo arm for ethical reasons due to overwhelming therapeutic benefit.
Limitations and Challenges
The biggest drawback: patients must remain on immunosuppressive drugs to prevent the destruction of the transplanted cells. Long-term immune suppression raises the risk of infections and may increase the risk of cancer. It’s possible that recipients may need to stay on these drugs for life.
According to The New York Times, this treatment is the culmination of 25 years of work that began when Harvard researcher Doug Melton’s son and daughter were both diagnosed with type 1 diabetes. The major hurdle was identifying the correct mix of chemical and biological signals to transform stem cells into islet cells. Harvard and other institutions reportedly invested over $50 million in this research. When Dr. Melton succeeded, Vertex took on the task of translating it to the clinic.
Vertex’s protocol, based on academic studies published between 2008 and 2015, uses a six-stage differentiation process to convert ESCs into mature, glucose-responsive β-cells. Although the full protocol is proprietary, the scientific community has identified over 50 differentiation factors involved, such as Activin A, WNT agonists, Notch inhibitors, and thyroid hormone. Full review here. This complexity likely makes Zimislecel a very expensive treatment, though pricing remains undisclosed.
How Does It Compare? Donislecel and Other Approaches
Another approved therapy for type 1 diabetes is Donislecel, developed by CellTrans Inc. and approved by the FDA in 2023. Donislecel uses fully differentiated pancreatic islet cells from deceased donors. Unlike Zimislecel’s renewable ESC-derived cells, Donislecel is limited by donor availability and variability.
A major advantage of Zimislecel is its potential for scalability: its stem cell-derived islet cells can be mass-produced with consistent quality. However, Zimislecel still requires immune suppression. A potential solution would be using autologous induced pluripotent stem cells (iPSCs) derived from the patient’s own body, which may avoid immune rejection. Unfortunately, iPSCs are expensive, time-consuming to produce, and carry risks such as incomplete reprogramming and tumor formation. Research is ongoing to address these limitations.
The Bigger Picture: Stem Cell Therapies Today
The FDA currently approves nine stem cell therapies, which include:
- Hematopoietic stem cell (HSC) transplants
- Cord blood products
- Gene-modified autologous HSC therapies
- Mesenchymal stromal cells (MSCs)
The first FDA-approved embryonic stem cell trial began in 2009 for spinal cord injury, sponsored by Geron. However, the trial was halted in 2011, allegedly due to a strategic pivot toward oncology. Its results were never published.
Hematopoietic stem cell transplants (HSCT)—either autologous (from the patient) or allogenic (from a donor)—are approved for over 80 conditions, including:
- Leukemias and lymphomas
- Childhood cancers like neuroblastoma
- Immune disorders and rare genetic diseases (e.g., Pearson syndrome, cartilage-hair hypoplasia)
Four gene-edited autologous HSC therapies are also approved, including:
- CRISPR-based therapy for sickle cell disease (2023)
- Therapy for metachromatic leukodystrophy (MLD) (2024)
The only approved MSC-based treatment is Ryoncil, used to treat pediatric steroid-refractory graft-versus-host disease.
Safety Concerns: Tumor Risk and Misconceptions
A major concern surrounding stem cell therapies is tumorigenicity. ESCs and iPSCs can, indeed, trigger formation of teratomas—disorganized tumors made of tissues from all three germ layers—because of their pluripotency. This is one reason Vertex uses rigorous, multilayered safety protocols before administering Zimislecel.
By contrast, mesenchymal stem cells (MSCs), including those derived from umbilical cord blood, have a strong safety profile. A 2023 review of 217 studies confirmed that MSCs do not form tumors. See review here.
Despite their safety, the FDA bans all non-approved uses of stem cells, including for joint pain, anti-aging, or chronic conditions. In 2021–2022, the agency formally withdrew enforcement discretion, making off-label stem cell use illegal in the U.S.
Global Landscape: Regulatory Differences
Other countries take a more flexible approach. In Mexico, for example, off-label and compassionate-use stem cell treatments are legal and overseen by the national regulator COFEPRIS. Countries such as the UAE, Israel, Argentina, and members of the EU are similarly supportive of cell therapy—provided that clinics obtain national regulatory approvals, verify laboratory sources, and track patient outcomes and side effects.