No Adult Stem Cells For Type I Diabetes?
By Suzanne Kadereit

In a mouse-model study published in the May 6, 2004 issue of Nature, Professor Douglas Melton and his team convincingly showed that new insulin-producing ß-cells in the pancreas are not generated by stem cells within the pancreas, but by the existing adult ß-cells¹. While it is known that many adult tissues contain stem cells that contribute to the regeneration of those tissues, scientists are still debating whether the pancreas contains stem cells that could regenerate the insulin-producing ß-cells.

Type I diabetes, or insulin-dependent diabetes, affects an estimated 5-10% of the18.2 million Americans with diabetes. In this disease, pancreas insulin-producing ß-cells are progressively destroyed by the immune system. Insulin produced by the pancreatic ß-cells controls blood sugar levels, preventing organ damage caused by excessive sugar levels in the blood. At a certain stage of the disease, patients will have to replace the insulin that is not produced by their pancreatic ß-cells, with insulin injections. The insulin injections are life saving, type I diabetics would die quickly without injections, but they are not an ideal long-term solution. It is very difficult to control blood sugar levels with injections as perfectly as the pancreas does. Type I diabetics are at risk of serious, sometimes life-threatening, organ damage in the whole body caused by their inappropriately regulated blood sugar levels.

It is hypothesized that the presence of stem cells within the pancreas could lead to cures for diabetes. Such stem cells could be isolated, grown in culture and new
ß-cells could be produced from them and transplanted into the patient. Alternatively, the stem cells could be stimulated with drugs within the intact tissue to divide and to produce ß-cells.

The recent work by Douglas Melton and his colleagues used an improved genetic labeling method where only adult ß-cells were permanently marked once they started to produce insulin. With this method stem cells were not labeled. Any ß-cells developing from these non-labeled stem cells would stay negative for the label, even once they started to produce insulin. By observing the number and distribution of the labeled cells within the pancreas over a long period of time, the group found no evidence of insulin-producing ß-cells generated from non-labeled cells. On the contrary, all ß-cells were generated from cells that expressed the genetic marker, strongly suggesting that they had been generated by division from ß-cells that already existed. While these findings do not absolutely rule out the existence of stem cells in the pancreas, they do show that such stem cells do not contribute to the generation of new ß-cells.

The findings of this report are important for two reasons. First, if ß-cells are not regenerated from adult stem cells in the pancreas, it is unlikely that a cure for diabetes could come from adult pancreatic stem cells. This brings embryonic stem cells back to the forefront as a possible treatment option for type I diabetes, because they are the only stem cells that have been shown to be able to generate insulin-producing b -cells. Second, now that it has been shown that ß-cells are generated by the division of already existing ß-cells, it may become feasible to restore pancreatic function in type I diabetics by activating the division of any remaining ß-cells. This, however, will require intense research into the regulation of ß-cell division to guarantee that the remaining ß-cells activated to divide and regenerate do not grow into a tumor. For type I diabetics with no remaining ß-cells, other treatment options will have to be developed, such as transplantation of ß-cells derived from embryonic stem cells, which is a technique that still needs to be refined.

Suzanne Kadereit, P.hD., is science editor of the ISSCR Web site.

1. Dor Y, Brown J, Martinez OI, Melton DA (2004). Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41-6.

Updated: February 2, 2005