Implantation of autologous induced pluripotent stem cell-derived islets provides long-term insulin independence in a patient with type 1 diabetes.

Type I diabetes (T1D) has long presented an attractive but elusive target for cellular therapy. Despite advances in insulin delivery, including wearable closed-loop systems, insulin therapy still provides suboptimal glycemic control, and long-term glucose level fluctuations continue to cause end-organ damage and life-threatening hypoglycemia. Conversely, strategies aimed at replacing beta cells lost to immune destruction, such as whole-pancreas and islet transplantation, face challenges related to limited donor tissue availability, technical complications, and long-term graft viability. Stem cells theoretically provide an unlimited source of insulin-producing cells, and have been the source of significant recent academic and industrial efforts. Indeed, in 2021, Vertex Pharmaceuticals began a phase I/II clinical trial transplanting embryonic stem cell-derived islets into the portal circulation of patients with T1D, and 17 patients have been treated to date with promising results—though the trial was recently voluntarily paused following two patient deaths deemed unrelated to the transplant. Still, concerns regarding the safety and efficacy of these therapies persist, particularly the risk of malignant transformation, the need for lifelong immunosuppression, and the ability to maintain long-term insulin independence.1 Further, embryonic stem cell-derived islets are allogeneic, and thus face the dual threats of both alloreactive and autoreactive immune responses. The promise of iPSC-derived islets is to circumvent at least the former of these limitations by developing islets from a patient’s own cells.