Aug. 31, 2000 IOWA CITY, Iowa -- University of Iowa researchers have found a way to improve circulation in the limbs of mice with diabetes. The findings have implications for the treatment of diabetes in humans. Poor circulation is the cause of many dangerous health problems in people with diabetes.
The research team led by Gina C. Schatteman, Ph.D., a research scientist in the UI Department of Anatomy and Cell Biology, discovered that injecting certain types of blood cells into the circulation-deficient limbs of mice with diabetes accelerated the restoration of blood flow to the limbs. The results were published in the Aug. 15 issue of the Journal of Clinical Investigation.
The UI study showed that a critical subset of blood cells, called angioblasts, taken from non-diabetic humans, helps to form new blood vessels in diabetic mice, and the rate of restoration of blood flow was faster than for untreated mice.
In humans, restoring blood flow to damaged tissue, generally a slow process, is made even slower by diabetes. People with diabetes do not grow new blood vessels in their limbs as well as people without the disease. The length of time it takes for a patient with diabetes to grow new blood vessels to replace damaged ones is a real problem; during this time the patient is in severe pain and at an increased risk of infection and gangrene, which can lead to amputation.
"The faster good blood flow can be restored to the limb, the faster you can alleviate pain and the more you can reduce the risk of the complications that arise from poor circulation," Schatteman said.
People with diabetes are also particularly susceptible to atherosclerosis (clogging of the arteries). The constricted blood vessels result in reduced blood flow to the limbs. This condition brings with it a host of problems such as poor wound healing ability.
In mice, where blood flow is normally restored relatively rapidly, the benefits of accelerated revascularization may not be obvious. However, in larger animals and humans, where restoration of flow is much slower, this acceleration may be of profound importance and could mean the difference between saving and losing a limb. Schatteman said that her team is currently investigating the use of these blood cells to restore flow in larger animal models.
Angioblasts are precursor cells that go on to become endothelial cells, the cells that line the walls of large blood vessels and form the walls of smaller blood vessels. Although the question of whether angioblast function is impaired in people with diabetes remains open, Schatteman’s study suggests that it is. Angioblasts from people with type I diabetes form fewer endothelial cells in culture than angioblasts from people without the condition. These findings suggest that the inability of these blood cells to become blood vessel wall cells contributes to certain vascular problems associated with diabetes.
Diabetes is a paradoxical disease. While people with this condition are less able to grow new blood vessels in the limbs than control subjects, they tend to grow more blood vessels in the eyes and kidneys. Too many blood vessels can be as problematic as too few, so any increase in revascularization needs to be targeted to the limbs.
"Our approach is designed to localize the revascularization to the limbs," Schatteman said. "We hope this approach will lead to fewer problems than a systemic approach, which would affect the whole body."
Schatteman cautioned that there are still many steps remaining to determine whether angioblasts may someday be useful therapeutic agents. An important first step will be to investigate the distribution of injected cells and examine the possible consequences of their incorporation into tissues beyond the site of injection.
While the current study focused specifically on restoring blood flow to a limb with damaged circulation, it is possible that the findings may be significant with respect to rapidly restoring blood flow to infarcted regions of the heart or to the brain after a stroke.
Researchers in the Department of Molecular Medicine at the University of Texas Health Science Center in San Antonio were also involved in this study. The research was supported by an American Heart Association -Texas Affiliate Grant-In Aid and a joint National Institutes of Health and Juvenile Diabetes Foundation International Grant.
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