Characterization of Human Pancreatic Beta-cell Progenitors as a Means to Alleviate the Shortage of Donor Tissue for Islet Transplantation

Abstract

The current shortage of islet tissue from cadaveric human donors is not sustainable and will preclude islet transplantation from becoming a widespread therapeutic treatment for those with type 1 diabetes. A potential alternative source of tissue may be through isolating, expanding, and differentiating beta-cell progenitors within the adult human pancreas. We sought to characterize the population of origin of beta-cell progenitors. Our human studies use pancreatic beta-cell progenitor marker, Pdx-1 to study the development and origin of beta-cells. In vivo immunohistochemical study of fetal development demonstrates morphologic evolution of islets throughout maturation and expression and interaction of several factors important to beta-cell development. In vitro study utilizes a novel cell culture media permitting long-term study of the epithelial population within the adult pancreas as well as lentiviral reporters and immunostaining to observe the differentiation of potential progenitor cells. Together our data suggests that Pdx-1 expressing progenitor cells are epithelial cells.