From pluripotent stem cells to bioengineered islets: A challenging journey to diabetes treatment.

Type 1 diabetes mellitus affects 45 million people worldwide and its prevalence is rapidly increasing. It derives from a lack of insulin production by the pancreas, which leads to elevated blood sugar levels. Current treatments rely on the administration of exogenous insulin, but they do not replicate the precise control of glycemia by the pancreas. Whole pancreas and pancreatic islet transplantation restore endogenous insulin secretion in response to blood glucose levels. However, both are limited by the lack of donors and the need for immunosuppressive therapy. Pluripotent stem cells are a virtually unlimited cell source and can be differentiated to the desired cell types. Moreover, induced pluripotent stem cells may be derived from the patient's cells, which could prevent graft rejection. Several protocols report the differentiation of pluripotent stem cells into insulin-producing cells that, after transplantation, can restore glycemic control. Such protocols are based on the embryonic development of the pancreas, highlighting the importance of understanding the different stages and signaling pathways involved in this process. Once the main hurdles to stem cell-based therapies are overcome, translation to clinical practice will greatly improve the quality of life of people with type 1 diabetes mellitus.