Posted by Allison on June 25, 2003 at 15:10:25:
Transplanted Bone Marrow Stem Cells Reverse Diabetes in Mice
New York, NY, June 25, 2003 — Researchers in Canada have shown that transplanted adult stem cells derived from bone marrow can induce the recipient’s pancreatic tissue to repair itself, restoring normal insulin production and reversing symptoms associated with diabetes. Although the study was done in mice, it raises the possibility that a similar treatment could at least partially reduce juvenile (type 1) diabetes in humans.
The most striking observation was that the stem cells themselves did not directly repair the pancreas; instead they appeared to recruit the transplant recipient’s own cells to multiply and begin to produce insulin in response to glucose. The mechanism through which the stem cells accomplish this is not yet known. The study, led by Mick Bhatia, Ph.D, of the John P. Robarts Research Institute, was reported online June 23 in the journal Nature Biotechnology.
In March, JDRF-funded researcher Mehboob A. Hussain, M.D., reported that some adult stem cells derived from the bone marrow of mice are capable, after transplantation, of giving rise to insulin-producing cells in the recipient animal’s pancreas. Those stem cells, however, appeared to turn into insulin-producing pancreatic beta cells. The new research suggests that bone-marrow derived stem cells send signals to existing organ cells — possibly the recipient’s own stem cells — and spur them to regenerate and produce insulin.
David Hill, Ph.D., scientific director of the Lawson Health Research Institute and a co-author on the paper, said in a press release that “the ability of marrow stem cells to induce a natural regeneration of the bodies’ own islets could in a future clinical context be more useful than islet transplantation, which is limited by organ donor supply.”
The Study
The researchers first created type 1 diabetes-like conditions in two groups of mice by destroying the animals’ insulin-producing beta cells with the chemical streptozotocin. Both groups had high blood glucose (hyperglycemia) as a result of the destruction. The researchers also exposed the mice to radiation, which effectively destroyed the animals’ bone marrow. Then stem cells derived from the bone marrow of nondiabetic mice were transplanted into the veins of one group of mice. After seven days, 85 percent of the mice that received transplants had blood sugar levels near normal. By contrast, a control group that did not receive transplants continued to have high blood sugar.
While more investigation is needed to identify and clarify the mechanism that spurred renewed insulin production, the finding may cause researchers to reassess the best way of using stem cells to treat diabetes. Most current effort is focused on finding ways to coax stem cells to develop into beta cells in a laboratory dish so they can be transplanted into a patient with diabetes. Researchers still are largely in the dark about how to do this.
Even if the bone marrow stem cell effect can be repeated in humans, researchers still would need to address the autoimmune attack that destroyed the original beta cells and presumably would destroy any that were regenerated. But there may be approaches to equipping the stem cells to forestall such an attack. As JDRF-funded researcher Len Harrison, M.D., D.Sc., reported last month, genetically modified stem cells prevented type 1 diabetes in mice by signaling the immune system not to attack the insulin-secreting beta cells.
In the ideal scenario, the transplanted stem cells would perform double duty, signaling the pancreas to make new islets and signaling the immune system to leave the islets alone once they develop. However, the research is in its very early stages, and many diabetes treatments that have worked in mice proved fruitless in humans.
“These novel observations holds exciting promise that approaches may be developed to activate endogenous islet cell regeneration in type 1 diabetes,” said Richard Insel, M.D., JDRF’s Executive Vice President for Research. “Application to type 1 diabetes, however, will require demonstrating that immune-damaged islets, as found in type 1 diabetes, behave similar to chemically damaged islets. Furthermore, host islet regeneration in type 1 diabetes will require that the ongoing immune destruction of islets is controlled with immunosuppressive therapy or by induction of immune tolerance, an area under active investigation by the JDRF. The JDRF will actively support further research in this new and promising line of investigation.”