Pancreatic cells and their progenitors.

Both type 1 and type 2 diabetes patients would greatly benefit from transplantation of insulin-producing pancreatic beta cells; however, a severe shortage of transplantable beta cells is a major current limitation in the use of such therapy. Understanding the mechanisms by which beta cells are naturally formed is therefore a central challenge for modern pancreas biology, in the hope that insights will be applicable for regenerative cell therapy strategies for diabetes. In particular, the cellular origins of pancreatic beta cells pose an important problem, with significant basic and therapeutic implications. This chapter discusses the current controversy regarding the identity of the cells that give rise to new beta cells in the adult mammal. Whereas numerous models suggest that beta cells can originate from adult stem cells, proposed to reside in the pancreas or in other locations, more recent work indicates that the major source for new beta cells during adult life is the proliferation of preexisting, differentiated beta cells. We present these different views, with emphasis on the methodologies employed. In particular, we focus on genetic lineage tracing using the Cre-lox system in transgenic mice, a technique considered the "gold standard" for addressing in vivo problems of cellular origins.