The incidence of diabetes mellitus (DM) is steadily increasing annually, with 537 million diabetic patients as of 2021. Restoring diminished β cell mass or impaired islet function is crucial in treating DM, particularly type 1 DM. However, the regenerative capacity of islet β cells, which primarily produce insulin, is severely limited, and natural regeneration is only observed in young rodents or children. Hence, there is an urgent need to develop advanced therapeutic approaches that can regenerate endogenous β cells or replace them with stem cell (SC)-derived or engineered β-like cells. Current strategies for treating insulin-dependent DM mainly include promoting the self-replication of endogenous β cells, inducing SC differentiation, reprogramming non-β cells into β-like cells, and generating pancreatic-like organoids through cell-based intervention. In this Review, we discuss the current state of the art in these approaches, describe associated challenges, propose potential solutions, and highlight ongoing efforts to optimize β cell or islet transplantation and related clinical trials. These effective cell-based therapies will generate a sustainable source of functional β cells for transplantation and lay strong foundations for future curative treatments for DM.
Impact Statement
The regenerative capacity of human β cells is extremely limited, and there is an urgent need to develop strategies to restore decreased β cell mass or impaired islet function. This review provides an outline of available cell-based strategies for treating insulin-dependent DM, including promoting the self-replication of endogenous β cells, inducing stem cell differentiation, reprogramming non-β cells into β-like cells, and generating pancreatic-like organoids through cell-based intervention, and discusses ongoing efforts to optimize β cell or islet transplantation and related clinical trials. We anticipate that increased knowledge of regenerating β cells will lead to the rational design of exciting cell-based therapies to cure diabetes, particularly T1DM.
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