Stem Cell-Derived Islets Functionally Cure Patient With Type 1 Diabetes

Investigators have released a preliminary analysis of a first-in-human study showing that stem-cell-derived islets functionally cured a patient’s type 1 diabetes (T1D), according to the analysis published in Cell. The analysis included 1 year of data, which assessed the feasibility of autologous transplantation of chemically induced pluripotent stem cell-derived islets. The islets were injected beneath the abdominal anterior rectus sheath, according to the study authors.¹

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The patient had sustained insulin independence 75 days post-transplant, with a time-in-target glycemic range increase from 43.18% at baseline to 96.2% at 4 months after transplantation. Combined with a decrease in glycated hemoglobin reaching approximately 5%, the patient presented with stable glycemic control.¹

In a review published in Stem Cell Research and Therapy in January 2024, the authors discussed the current state of stem cell therapy for T1D as well as challenges with the therapy. Of note, investigators have developed protocols to differentiate pluripotent stem cells into pancreatic progenitors or fully differentiated β-cells, which have shown control of chemically induced diabetes. One challenge with these cells is the need for an immunoisolation device and/or immunosuppressive as needed, according to the authors of the review.²

Additionally, there have been a growing number of studies focused on genetic manipulation to produce immune evasive cells, but the authors note the evidence needs to show that the genetic manipulation does not lead to any unforeseen complications. For mesenchymal stem/stromal cells (MSC), investigators note that these can form insulin-producing cells, which show that transplantation of allogenic insulin-producing cells from MSCs are associated with muted allogenic response without interfering with functionality.²

Furthermore, exosome derived from naïve MSCs have also been shown to have varying degrees of success in rodent models, including a reduction in insulin resistance, promotion of autophagy, and increase in T regulatory populations.²

In June 2023, the FDA approved the first allogeneic pancreatic islet cellular therapy, donislecel (Lantidra; CellTrans), comprised of deceased donor pancreatic cells. It is approved for individuals with T1D who are unable to approach the target glycated hemoglobin due to repeated episodes of severe hypoglycemia, despite intensive diabetes management and education. The primary mechanism of action is the secretion of insulin by infused allogenic islet β-cells, which can sometimes produce enough insulin that the patient no longer needs to take insulin to control their blood sugar.³

Furthering the potential of stem cells for the treatment of T1D, new data from the phase 1/2 FORWARD clinical study were presented at the American Diabetes Association 84th Scientific Session in Orlando, Florida, in June 2024. The results showed the VX-880 reduced or eliminated the need for insulin use for patients with T1D, further showing that stem-cell-derived islets can restore physiological islet function and improve glycemic control.⁴

REFERENCES

1. Wang S, Du Y, Zhang B, et al. Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. Cell. Published online September 20, 2024. doi:10.1016/j.cell.2024.09.004

2. Ghoneim MA, Gabr MM, El-Halawani SM, Refaie AF. Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration. Stem Cell Res Ther. 2024;15(1):23. Published 2024 Jan 29. doi:10.1186/s13287-024-03636-0

3. FDA Approves First Cellular Therapy to Treat Patients With Type 1 Diabetes. News release. FDA. June 28, 2023. Accessed October 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type-1-diabetes

4. Expanded FORWARD Trial Demonstrates Continued Potential for Stem Cell-Derived Islet Cell Therapy to Eliminate Need for Insulin for People With T1D. News release. American Diabetes Association. June 21, 2024. Accessed October 8, 2024. https://diabetes.org/newsroom/press-releases/expanded-forward-trial-demonstrates-continued-potential-stem-cell-derived