Stem-cell therapy for diabetes mellitus.

CONTEXT: Curative therapy for diabetes mellitus mainly implies replacement of functional insulin-producing pancreatic beta cells, with pancreas or islet-cell transplants. However, shortage of donor organs spurs research into alternative means of generating beta cells from islet expansion, encapsulated islet xenografts, human islet cell-lines, and stem cells. Stem-cell therapy here implies the replacement of diseased or lost cells from progeny of pluripotent or multipotent cells. Both embryonic stem cells (derived from the inner cell mass of a blastocyst) and adult stem cells (found in the postnatal organism) have been used to generate surrogate beta cells or otherwise restore beta-cell functioning. STARTING POINT: Recently, Andreas Lechner and colleagues failed to see transdifferentiation into pancreatic beta cells after transplantation of bone-marrow cells into mice (Diabetes 2004; 53: 616-23). Last year, Jayaraj Rajagopal and colleagues failed to derive beta cells from embryonic stem cells (Science 2003; 299: 363). However, others have seen such effects. WHERE NEXT? As in every emerging field in biology, early reports seem confusing and conflicting. Embryonic and adult stem cells are potential sources for beta-cell replacement and merit further scientific investigation. Discrepancies between different results need to be reconciled. Fundamental processes in determining the differentiation pathways of stem cells remain to be elucidated, so that rigorous and reliable differentiation protocols can be established. Encouraging studies in rodent models may ultimately set the stage for large-animal studies and translational investigation.