Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?

Abstract

Diabetes is a chronic metabolic disease caused by an absolute or relative deficiency in functional pancreatic β-cells that leads to defective control of blood glucose. Current treatments for diabetes, despite their great beneficial effects on clinical symptoms, are not curative treatments, leading to a chronic dependence on insulin throughout life that does not prevent the secondary complications associated with diabetes. The overwhelming increase in DM incidence has led to a search for novel antidiabetic therapies aiming at the regeneration of the lost functional β-cells to allow the re-establishment of the endogenous glucose homeostasis. Here we review several aspects that must be considered for the development of novel and successful regenerative therapies for diabetes: first, the need to maintain the heterogeneity of islet β-cells with several subpopulations of β-cells characterized by different transcriptomic profiles correlating with differences in functionality and in resistance/behavior under stress conditions; second, the existence of an intrinsic islet plasticity that allows stimulus-mediated transcriptome alterations that trigger the transdifferentiation of islet non-β-cells into β-cells; and finally, the possibility of using agents that promote a fully functional/mature β-cell phenotype to reduce and reverse the process of dedifferentiation of β-cells during diabetes.

Type 1 diabetes – What’s new in prevention and therapeutic strategies?

“…Enzymatic digestion, controlled gentle mechanical shear, purification, and culture is the established approach to preparation of a final enriched islet cell product that is considered safe for intra-portal infusion of the recipient's liver [55]. The problem, however, is still obtaining cells for transplantation, as well as their protection against destruction processes after transplantation [56][57][58][59]. Recently, an extensive discussion of methods for harvesting cells in animal models has also been presented [60,61].…”

DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development

“…5 , 6 While successful methods have been developed to replace β-islet cells through transplantation or regenerative therapies, the islet cells remain susceptible to attack by autoreactive T cells. 8 , 9 Thus, an effective cure for T1D would require pancreatic islet cell replacement, as well as inhibition of autoreactive T cells, while sparing pathogen- and tumor-specific T cells.…”