Cell therapy for type 1 diabetes: Tracing historical progress and exploring emerging technologies

Type 1 diabetes remains an incurable autoimmune disease, and despite advances in insulin-delivery systems, many patients still face severe hypoglycemia, glucose variability, and psychological burden. Beta-cell replacement offers a transformative alternative, with allogeneic islet transplantation providing durable protection and improved quality of life, yet limited by donor availability and the need for immunosuppression. Stem cell-derived islet-like clusters are now reaching clinical milestones, showing promising insulin independence and glycemic control, while encapsulation, autologous induced pluripotent stem cells (iPSC)-derived therapies, and gene-edited "hypo-immune" cells aim to overcome immune barriers. Porcine islet xenotransplantation is also being revisited, although regulatory and immunological hurdles remain. Key challenges persist in cell delivery, engraftment, and long-term function. As cell therapy transitions from experimental proof-of-concept to clinical reality, success will require scalable manufacturing, safe and effective delivery, regulatory alignment, and patient-centered approaches to ensure broad and meaningful impact.