Lineage-Committed Pancreatic Progenitors and Stem Cells

Type 1 diabetes is an autoimmune disease where self-reactive T cells attack and destroy insulin-producing beta cells. The prevalence of type 1 diabetes is increasing worldwide, but therapeutic options to cure diabetes are presently restricted to transplantation of cadaveric insulin-producing (islet) cells. One of the limitations to success of islet transplantation therapy is the lack of donor pancreatic islets. An alternative is to generate insulin-producing (β-like) cells in the laboratory. Various sources of stem/progenitor cells, such as those from the umbilical cord blood, bone marrow, as well as embryonic stem (ES) cells/induced pluripotent stem (iPS) cells, have been tested for their potential to differentiate into an endocrine pancreatic lineage. These studies have confirmed that it is very difficult to generate a cell type that is able to produce physiologically significant amounts of insulin and secrete it in response to glucose, in a manner similar to that demonstrated by pancreatic beta cells. This chapter reviews the differentiation and commitment of adult pancreatic progenitor/stem cells to endocrine pancreatic lineage and discusses the practical difficulties towards using these for treatment of diabetes in humans.