Abstract
The quest for therapies that can normalize blood glucose control and provide independence from exogenous insulin could impact the life of millions of patients with type 1 diabetes (T1D) and a significant subset of patients with type 2 diabetes (T2D) with a functional deficiency in insulin production. Islet transplantation could be considered the first clinically successful cell therapy for T1D, but its widespread application is still hampered by the need for immunosuppression and the scarcity of organs available for processing and transplantation. The existence of these roadblocks has fostered the development of alternative approaches aimed at identifying high-yield sources of insulin-producing cells. Here we will discuss the state of the art in regenerative therapies for pancreatic islets, from stem cells to reprogramming. An outlook of the pancreatic development blueprint will help us in understanding key steps of stem cell differentiation, guiding us in the design of clinically translatable strategies. Major hurdles remain to be overcome for these approaches to find their way to the clinic: of these, we will specifically emphasize yield, safety, and immunological challenges.
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