New studies in the laboratory of Dr. Darwin J. Prockop, Director of Tulane University's Center for Gene Therapy, are shedding light on the previously mysterious mechanism through which even relatively small amounts of stem/progenitor cells taken from a patient's own bone marrow enhance repair of damaged tissues.
The cells not only differentiate to replace injured cells, as had been understood, but they also stimulate the proliferation and differentiation of stem cells already present in the injured tissue and they transfer mitochondrial DNA to local cells in which the mitochondria (the energy of the cell) is not working. Better understanding of the different mechanisms of these stem/progenitor cells suggests multiple strategies for developing new therapies for a broad range of diseases, says Dr. Prockop. It also may help make such treatments more effective and minimize potential dangers.
Dr. Prockop was the keynote speaker at the American Association of Anatomists meeting in Washington, DC., held as part of Experimental Biology 2007. His talk is Sunday, April 19.
Dr. Prockop described two series of experiments. In the first studies, human stem/progenitor cells were injected into the hippocampal region of the brain in immunodeficient mice. The human stem/progenitor cells increased the growth and differentiation of stem cells normally found in the brains of mice and other animals. In the second studies, when human stem/progenitor cells were intravenously infused into mice that had been made to have a disease similar to human diabetes, the stem/progenitor cells traveled to and engrafted themselves in the pancreas. There, they increased the growth of the stem cells normally found in the pancreas, producing more islet cells, thus increasing the mice's production of insulin, and lowering blood sugar. With some tissue damage, the administered cells are able to do their repair activities in as little as a day and largely disappear.
The scientists could still see cells after a month in the mice with diabetes - but not in normal mice that had received similar injections. The scientists were especially surprised and pleased to see that the stem/progenitor cells also engrafted into the kidney of the mice with the diabetes-like disease. In the kidney, the human stem/progenitor cells appeared to repair the microscopic damage that usually occurs in diabetes.
Dr. Prockop believes these results suggest possible new treatments for people with diabetes - there would be no problem getting healthy stem cells from their bone marrow - and especially for the 8 million people in the United States alone whose worsening diabetes is causing kidney failure.
Dr. Prockop also is pleased that the studies are explaining the mechanisms by which the cells work, in animals and in the more than 1,000 cardiovascular and other patients in the United States believed to be enrolled in clinical trials using these cells taken from their bone marrow. For such patients, the experimental treatment is their only option, but as the treatments are made available to larger numbers of people across a variety of different diseases it will be increasingly necessary to proceed carefully, says Dr. Prockop, and good basic science research will be critical. The Tulane Center for Gene Therapy is the only National Institutes of Health-designated center to distribute human stem cells (taken from healthy volunteers who give small samples of bone marrow from which to clone the cells) and from mice. Currently more than 270 scientists in the United States and other countries are working with the Tulane cells, meaning that research studies all are using well-standardized cells.
The research described at the Experimental Biology meeting is supported in part by grants from the National Institutes of Health, HCA the Healthcare Company and the Louisiana Gene Therapy Research Consortium.