Abstract
Diabetes mellitus (DM) is a metabolic disease characterized by persistent hyperglycemia, resulting from defects in insulin secretion or impaired insulin action. In cases of severe pancreatic cell dysfunction and deficiency, the primary treatment remains lifelong insulin injections. A potential alternative is allogeneic pancreatic cell transplantation from a donor, which can stabilize glucose levels. However, the scarcity of donor material and the risk of immune rejection limit the widespread use of this approach. An alternative solution involves using in vitro-derived insulin-producing cells generated through the differentiation of pluripotent stem cells (PSCs), which could overcome the shortage of transplantable material. Furthermore, patient-specific cells-obtained directly from the patient via reprogramming of blood or skin cells into induced pluripotent stem cells (iPSCs)-would avoid immune rejection. Advances in this field have led to the active development and optimization of PSC differentiation into hormone-producing cells worldwide, with more than hundred patients dosed in clinical trials with ESC-derived cells and the single trial of iPSC-derived cells. This review highlights recent progress and prospects in generating insulin-producing cells from human PSCs, their applications in therapy development and disease modeling, as well as the current challenges and potential solutions.