Insights into the development of insulin-producing cells: Precursors correlated involvement of microRNA panels

Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by the destruction of pancreatic β cells, recently estimated to affect approximately 8.75 million individuals worldwide. At variance with conventional management of T1D, which relies on exogenous insulin replacement and insulinotropic drugs, emerging therapeutic strategies include transplantation of insulin-producing cells (IPCs) derived from stem cells or fully reprogrammed differentiated cells. Through the in-depth analysis of the microRNAs (miRNAs) involved in the differentiation of human embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs), into insulin-producing cells, this review provides a comprehensive overview of the molecular mechanisms orchestrating the transformation of precursors to cells producing insulin. In addition to miR-375, involved in all differentiation processes, and to miR-7, mir-145 and miR-9, common to the generation of insulin-producing cells from at least two different sources, the literature reveals panels of miRNAs closely related to precursor cells and associated with specific events of the physiological β cell maturation. Since the forced modulation of miRNAs can direct cells development towards insulin-producing cells or modify their fate, a more comprehensive knowledge of the miRNAs involved in the cellular events leading to obtain efficient β cells could improve the diagnostic, prognostic, and therapeutic approaches to diabetes.