β cell regeneration

Replacing the 350 million β cells destroyed in people with type 1 diabetes has traditionally been sought by transplanting human pancreatic tissue obtained after death. Alternative sources of exogenous surrogate β cells being examined include stem cells, fetal pancreas and cells derived from the liver, with pluripotent stem cells offering the most hope for a large supply of usable tissue. Whilst induced pluripotent stem cells offer the benefit of being autologous, genetic manipulation required for their formation creates safety concerns for future therapeutic use. Encapsulation of pancreatic progenitors derived from embryonic stem cells seems to offer a solution allowing acceptance of the histoincompatible cells, and prevention not only of teratomas but also recurrence of autoimmune rejection.Regenerating β cells from non-β cells in the endogenous pancreas is being attempted using several agents, with most promise ones arising from the administration of gastrin and an incretin. The peptide INGAP, or its humanized version, HIP, also may be beneficial. At present, more benefit has been achieved in rodents, but clinical trials are underway. The main source of new β cells in humans is from pancreatic progenitors, whereas in rodents it is from pre-existing β cells.

Section editor:Jay Edelberg – Bristol-Myers Squibb Co, Pennington, NJ 08534, USA