21 Pancreatic Stem Cells

Abstract

β-CELL LOSS: A TERMINAL PROCESS Insulin-dependent, or type I, diabetes mellitus (IDDM) is a devastating disease in which affected individuals depend on daily injections of exogenous insulin for regulation of glucose homeostasis and survival. The lifetime dependency on insulin invariably leads to a variety of debilitating complications that threaten quality of life and significantly shorten life expectancy of IDDM patients. Insulin-producing cells in the pancreatic islets of Langerhans are the targets for selective inflammatory destruction in IDDM. This loss of the pancreatic islets is a terminal process, since the pancreas lacks any significant ability to regenerate insulin-producing cells. Indeed, pancreatic islet cells have a very low rate of growth in adults, and knowledge of the factors that regulate islet growth is lacking. Increased knowledge of islet stem cells and potential islet regeneration could allow critical advances in the development of new therapies for IDDM. Knowledge regarding pancreatic stem cells has grown dramatically in recent years, but continued progress is still hampered by the lack of in vitro and in vivo assay systems for stem cell activity and function. In this review, we focus on pancreatic stem cells during morphogenesis and regeneration, as well as on the molecular markers associated with these cells. ONTOGENY OF PANCREATIC ENDOCRINE CELLS During embryogenesis, the pancreas arises from the foregut, initially as two distinct bulges on either side of the duodenum, termed the dorsal and ventral buds (for review, see Slack 1995). The two buds grow independently, with both endocrine and exocrine tissue components present...