Rat Liver Stem Cells Can Become Insulin-Producing
University of Florida scientists report today that adult rat liver stem cells can evolve into insulin-producing pancreatic cells, a finding that has implications for the future of diabetes research.
Preliminary studies also show that the cells, when injected into diabetic mice, are able to reverse the animals' high blood-sugar levels, the researchers wrote in today's online edition of Proceedings of the National Academy of Sciences. The article will appear in print June 11.
"Our major observation from this work is that adult stem cells from a non-pancreatic source can be pushed into becoming mature cells capable of producing and secreting insulin in response to glucose without genetically altering the mature cells," said UF pathologist Dr. Lijun Yang, who spearheaded the work, funded by the National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with UF scientists Ammon B. Peck and Bryon E. Petersen.
The discoveries raise the possibility the liver could someday serve up a steady supply of cells with the potential to secrete insulin for patients with diabetes.
"I think this study shows tremendous promise for the use of liver-derived cells to treat diabetes," said Dr. Diane Krause, an associate professor of laboratory medicine at Yale University School of Medicine. "It is important to note that this work represents a breakthrough that was built from extensive prior research on stem cells and the study of embryonic development."
Insulin-dependent, or type 1, diabetes occurs when white blood cells vital to the body's defenses against infectious diseases launch a self-directed, or autoimmune, attack on insulin-producing cells in the pancreas. The cells that produce insulin regulate how the body uses and stores sugar and other food nutrients for energy.
More than 1 million Americans are estimated to have the disease. Many suffer major side effects, including damage to blood vessels, which can lead to heart disease, stroke, blindness, kidney failure and poor circulation to the lower limbs."In general, it has long been thought that blood stem cells could only make blood, and liver stem cells were born in the liver and could only make liver, and so forth," said Petersen, who is part of a multidisciplinary stem cell team that includes members of UF's McKnight Brain Institute and the UF Shands Cancer Center. "We were asking the question: Could liver stem cells be changed into a different cell type? Our latest findings basically show the flexibility of adult stem cells. We are now starting to understand how these cells work at the molecular and cellular levels and how to utilize this information to our advantage."
UF research previously reported by Peck in the journal Nature Medicine demonstrated that type 1 diabetes could be reversed in mice by nurturing adult pancreatic stem cells in a test tube until they grew into insulin-producing organs called islets of Langerhans, then injecting the islets just beneath the skin. The implanted islets soon produced enough insulin to regulate blood sugar effectively.
In the current study, UF scientists isolated cells from the adult rat liver, then placed them in a high-sugar solution. The cells began to produce insulin, which liver cells don't normally do. Researchers subsequently implanted the cells into a small number of diabetic mice. Blood-sugar levels dropped to normal within 10 days in one mouse that had been given a high number of insulin-producing cells. Another two mice received much smaller numbers of cells and remained diabetic.
"In recent years, there has been a great deal of excitement for treating diabetes with islet injections," Peck said. "Unfortunately, there is a major shortage of available islet tissue for injection, and this has led to an increase in efforts to search for alternative sources of insulin-producing cells. Adult stem cells appear to offer great promise for the production of an almost unlimited supply of insulin-producing cells and islets of Langerhans.
"The ability to grow insulin-producing cells from liver stem cells shows the remarkable potential of adult stem cells for future cell therapy," he added. "The ultimate goal is to be able to grow insulin-producing cells from the patients' own stem cells for treating their diabetes, and this will most likely require stem cells from a non-pancreatic source, such as the liver or bone marrow."
UF researchers currently are evaluating how long these cells will survive and function as insulin-producing cells, and precisely how effective they are at reversing diabetes in animal models, Yang said.
"A major question is whether one injection of cells will last a lifetime or whether several injections will be needed," she said. "Another question is whether the change in the cell type is permanent or whether the cells can revert to liver cells. There are still many questions to be answered." - By Melanie Fridl Ross
[Contact: Melanie Fridl Ross]
04-Jun-2002 |
