Beta Cell Regeneration

Luc      Bouwens

Abstract

Beta cell replacement and regeneration therapies seem promising approaches to the treatment of insulindependent diabetes. The short supply in beta cells from cadaveric organ donors and the very low replication capacity of human beta cells have spurred efforts to find robust ways of (re-)generating beta cells in vitro and in vivo. In the pancreas, both the capacity of regeneration and the mechanism involved can differ significantly depending on the experimental model, as it has also been found in other organs like the liver. Robust expansion of the beta cell mass in adult rodent pancreas doesnt normally occur after partial (50-70%) pancreatectomy nor after beta cell destruction by streptozotocin or alloxan. However, extensive tissue injury and treatment with certain gastrointestinal hormones, like gastrin and growth factors from the EGF-family can stimulate beta cell regeneration. Whereas a slow rate of beta cell mass expansion can result from beta cell replication, more robust regeneration depends largely on neogenesis from precursor cells. Precursor cells can be derived from stem cells or from pancreatic exocrine cells which are known to retain phenotypic plasticity and can transdifferentiate into, amongst others, endocrine cells. Identifying the conditions involved in the regulation of cellular plasticity and regenerative growth may lead to new pharmacological strategies for the treatment of diabetes.

Keywords: Islets of Langerhans, Neogenesis, Stem cells, Metaplasia, Pancreas, Diabetes