Journal Review: Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes
By John Joseph Pack MD
Published on 09/15/2025
Original Source: New England Journal of Medicine, September 4, 2025, vol 393, no. 9, pg. 858-868
Independent, original summary by John Joseph Pack MD
This important study, funded by Vertex Pharmaceuticals, and administered by a number of national and international academic centers, employed a novel allogeneic stem cell-derived islet cell therapy, called Zimislecel, or VX-880, in patients with type 1 diabetes mellitus. Type 1 diabetes is typically an auto-immune disease which destroys B-cell function in the pancreatic islets leading to chronic hyperglycemia and high morbidity and mortality over the patient's lifetime, which is often considerably reduced.
During this multi-part study, VX-880, or Zimislecel, designed to engraft specific allogeneic stem cells into human tissue, was injected into the hepatic portal vein in 14 participants in an effort to see if pancreatic islet cell function could be restored. C-peptide levels, which measure endogenous insulin production, were non-existent in all 14 participants prior to the study. By day 365, 83% had achieved insulin independence and had hga1c levels less than 7%. There were no hypoglycemic events reported once the participants were off exogenous insulin, indicating both Alpha-cells and Beta-cells were working in conjunction with each other and all had detectable C-peptide levels.
Two patients died during the study. One from Cryptococcal meningitis which occurred after a complicated sinus surgery in which the cribriform plate was breached and the other from progressive dementia, which was a pre-existing condition. It is unclear why that patient qualified for the study. Patients were given non-steroidal immunosuppressants to prevent rejection.
The results of this study, and the significance of the novel agent, VX-880, an allogeneic stem cell differentiated into a Beta-cell, suggests type 1 diabetes may, in the near-future, be able to be reversed and cured using this technology, leading to a substantial reduction in morbidity and mortality among those suffering from the disease. How long immunosuppressants must be taken for afterwards, and whether auto-immune Beta-cell destruction will recur down the road, are yet to be investigated. This work looks promising, and something to build on.
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