Generation of Islets from Pancreatic Progenitor Cells

results from an inadequate supply of insulinproducing β cells. Transplantation of islets isolated from cadaver pancreata has become more successful with new protocols and immunosuppressive drugs.1,2 However, new sources of insulin-producing cells must become available to extend β-cell replacement therapy to more of the thousands of patients with diabetes. Because the β cell is the cell lacking in diabetes, it is generally assumed that the replacement of just the β cell may be sufficient, but clear evidence is still lacking. As late as two decades ago, it was still commonly thought that one was born with all the β cells that one ever had; however, it has become clear that the mass of pancreatic β cells is dynamic and is regulated in an effort to maintain euglycemia.3–5 A number of in vivo models have provided evidence that there is a cell renewal process (both replication and neogenesis) that occurs at low levels in normal adult rodents and can be stimulated greatly by experimental conditions. This latter case is what should be considered regeneration; it is likely, but still needs rigorous evidence, that normal growth and regeneration in response to injury or to increased stimulation involve the same progenitor cells and the same pathways. Understanding the regulation of the normal process may lead to new therapies for diabetes that involve generation of new islets either in vitro for transplantation or in vivo by stimulation of the endogenous pancreas. We will use replication to indicate the mitotic division of a cell already with a β cell phenotype and neogenesis to indicate the formation of new β cells from either progenitor or stem cells.