Reviewing Major Mechanisms of β-Cell Regeneration: A Prospective Treatment for Diabetes Mellitus

Abstract

Regeneration of human pancreatic β cells has the direct ability to treat type 1 and type 2 diabetes mellitus because important characteristics of diabetes include compromised function and/or reduced mass of β cells. While there has been limited success in transplanting pancreatic islets to supplement β cells in patients with diabetes, the low supply of donors requires a continuation of the search for sustainable sources of β cells. Research investigating different mechanisms of β-cell regeneration has been promising. First, neogenesis of β cells in vivo can be conducted by precisely differentiating embryonic stem cells and induced pluripotent stem cells. Second, duplication of β cells occurs in vivo but significantly slows down after infancy. Studies using animal models have suggested ways to induce β-cell duplication in the adult pancreas. Third, the potential to induce endogenous transdifferentiation of other mature pancreatic cells into β cells has recently attracted attention, especially in research involving the use of α cells as progenitor cells. This review summarizes the 3 major mechanisms through which β cells are regenerated and discusses the challenges associated with translating this research into clinical therapeutics for patients with diabetes. Furthermore, current findings suggest that transdifferentiation of existing pancreatic progenitor cells has the most potential as a source of β cells in this field of regenerative medicine.