Generating pancreatic endocrine cells from pluripotent stem cells

Abstract

Human islet transplantation shows considerable promise as a physiological means of insulin replacement for type 1 diabetes, although donor availability and progressive loss of graft function continues to hamper more widespread implementation. Pluripotent stem cells (PSCs) by definition have the ability to form all tissues of the body including insulin-secreting pancreatic β-cells. This potential has led many academic and industry groups to examine methods for efficient production of functional insulin-producing cells from PSCs. Engineered in vitro differentiation protocols generally mimic known pancreatic developmental cascades, which convert undifferentiated cells, through germ-layer specification, to restricted pancreatic endodermal progenitors. The continued development of these progenitors in vivo results in the formation of functional pancreatic endocrine cells capable of preventing and/or reversing diabetic hyperglycemia in rodent models. While the insulin-producing, antidiabetic capacity of differentiated PSCs is very promising, key questions remain about optimizing differentiation processes for functional in vitro maturation, as well as whether production of pancreatic endocrine tissue is reproducible on a clinical scale and sufficiently safe. With additional research and development in these areas, the induction of differentiation processes to yield pancreatic endocrine-like cells could yield a potentially limitless supply of functional β-cells capable of replacing current human islet transplantation therapies for diabetes.