Can Functionally Mature Islet β-Cells be Derived from Pluripotent Stem Cells? A Step Towards Ready-To-Use β-Cells in Type 1 Diabetes

Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for the treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer's disease, etc. PSC-derived pancreatic islet beta-cells appear to be a promising therapy for type 1 diabetic patients with impaired beta-cell function. Several protocols have been developed to derive beta-cells from PSCs. However, these protocols produce beta-like cells that show low glucose stimulated insulin secretion (GSIS) function and mirror GSIS profile of functionally immature neonatal beta-cells. Several studies have documented a positive correlation between the sirtuins (a family of ageing-related proteins) and the GSIS function of adult beta-cells. We are of the view that the GSIS function of PSC-derived beta-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the beta-cell development and inclusion of the sirtuin activators and inhibitor cocktail (specific to a developmental stage) in the present protocols may help us derive functionally mature, ready-to-use beta-cells in-vitro making them suitable for transplantation in type 1 diabetes.