Pancreatic stem cells

Controversy over whether pancreatic islet cells arise from adult stem or progenitor-like cells actually predates the discovery of insulin, and the recent use of islet transplantation to treat diabetes has only intensified interest in this question. Recent breakthroughs, particularly those based on Cre-loxP lineage-tracing in the mouse, have resolved some aspects of this controversy, but not all. We now know that insulin-producing βcells and other islet cells derive from multipotent progenitors in the embryo, but that their maintenance and expansion in postnatal life is driven primarily by proliferation of existing differentiated cells. This appears to be true even during regeneration, and seems to apply to the exocrine acinar cells as well as islets. Following pancreatic duct ligation, however, islet precursors re-appear in the injured pancreas, arising from ducts and differentiating into new islet cells. Thus, while the pancreas does not normally rely on classical stem cells, a stem cell-like mechanism for new islet differentiation may be inducible under specific circumstances. Understanding the signals that promote β-cell formation in the embryo and adult should facilitate efforts to derive clinicallyuseful β-cells in vitro, either from adult ducts or embryonic stem cells.