Restoring β Cells Population Through In Situ Differentiation of Residential Pancreatic Cells

Diabetes mellitus (DM) is a global health problem leading to morbidity, mortality, and compromising the quality of life. DM is well characterized by an irreversible loss of β cells leading to hyperglycemia and associated secondary complications such as nephropathy, neuropathy, and retinopathy. Current therapeutic strategies improve glucose homeostasis without restoring the β cell mass. One of the critical pathophysiological events is the reduction in β cell mass due to dedifferentiation enforced by the nutritional, endoplasmic reticulum, and oxidative stress. This book chapter summarizes the opportunities to replace declining β cell mass and function through transdifferentiation of residential pancreatic cells such as α, δ, acinar, and ductal cells. Furthermore, resident mesenchymal stem cells (MSCs) can be differentiated into insulin-producing cells. These cells share standard developmental programming and exhibit a similar epigenetic profile to that of β cells, rendering them an ideal in situ cell source to replenish the β cells. Recent advances in bioengineering have offered tools for screening novel and repurposed drugs that can mediate the transdifferentiation of these cells into functional β cells. Moreover, small molecules capable of transdifferentiating α, δ, acinar, ductal cells, and resident pancreatic MSCs into optimally functional β cells could emerge as a sustainable therapeutic solution to the increasing progression of DM.