Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells

Abstract

Islet transplantation, including pancreatic beta cells, has become an approved treatment for type I diabetes. To date, the number of donors limits the availability of treatment. Induction of pancreatic endocrine cells from pluripotent stem cells including iPSCs in vitro offers promise as a solution, but continues to face problems including high reagent costs and cumbersome differentiation procedures. In a previous study, we developed a low-cost, simplified differentiation method, but its efficiency for inducing pancreatic endocrine cells was not sufficient: induction of endocrine cells is non-uniform, resulting in colonies containing relatively high ratio of non-pancreatic-related cells. Here, we applied cyclin-dependent kinase inhibitors (CDKi) within a specific time window, which improved the efficiency of pancreatic endocrine cell induction. CDKi treatment reduced the prevalence of multi-layered regions and enhanced expression of the endocrine progenitor–related marker genes PDX1 and NGN3 resulting in enhanced production of both INSULIN and GLUCAGON. These findings support a step forward in the field of regenerative medicine of pancreatic endocrine cells.