Current status of islet cell replacement and regeneration therapy.

Context: Beta cell mass and function are decreased to varying degrees in both type 1 and type 2 diabetes. In the future, islet cell replacement or regeneration therapy may thus offer therapeutic benefit to people with diabetes, but there are major challenges to be overcome.

Evidence Acquisition: A review of published peer-reviewed medical literature on beta-cell development and regeneration was performed. Only publications considered most relevant were selected for citation, with particular attention to the period 2000-2009 and the inclusion of earlier landmark studies.

Evidence Synthesis: Islet cell regenerative therapy could be achieved by in situ regeneration or implantation of cells previously derived in vitro. Both approaches are being explored, and their ultimate success will depend on the ability to recapitulate key events in the normal development of the endocrine pancreas to derive fully differentiated islet cells that are functionally normal. There is also debate as to whether beta-cells alone will assure adequate metabolic control or whether it will be necessary to regenerate islets with their various cell types and unique integrated function. Any approach must account for the potential dangers of regenerative therapy.

Conclusions: Islet cell regenerative therapy may one day offer an improved treatment of diabetes and potentially a cure. However, the various approaches are at an early stage of preclinical development and should not be offered to patients until shown to be safe as well as more efficacious than existing therapy.