Researchers Discover Blood Stem Cells

Stem cells found in the bone marrow of adult mice don't just evolve into key components of bloodthey are able to build blood vessels. The discovery, announced on 5/31/02 by University of Florida scientists writing in the online edition of Nature Medicine, marks an important step in the quest to master diabetes, cancer, heart disease, sight-robbing retinal disorders and a multitude of other medical conditions.

The bone marrow is a rich source of stem cells, long heralded for their ability to mature into red and white blood cells and platelets. And as the key ingredient in a bone marrow transplant, stem cells already play a critical role in treating bloodborne cancers like leukemia.

The latest findings open new lines of inquiry for scientists scrutinizing diseases involving excessive blood vessel growth, diseased arteries or other circulatory troubles. Doctors might someday be able to use the knowledge to encourage growth of new blood vessels that could repair injured organs or tissues or, alternatively, stop such growth when it could harm rather than help, said Edward Scott, an associate professor of molecular genetics at the UF Shands Cancer Center and director of the Program in Stem Cell Biology at UF's College of Medicine.

"We've shown for the first time that adult blood stem cells can function to make blood vessels. We now know blood vessels can be formed from a remote locationthey're not just repaired at the site of injury," Scott said. "That means we can now explore how to block that from happening to try to prevent things like diabetic retinopathy or enhance that activity to promote new blood vessel formation or blood vessel repair."

UF scientists said the breakthrough came through studies of more than 100 mice that were models for the human eye condition known as retinopathy. This diabetes-related complication, the leading cause of adult blindness in the United States, is characterized by a degenerative process that injures existing blood vessels and triggers new capillaries to form as the body struggles to repair the light-sensing retina. These new capillaries actually foster additional damage.

The mice received bone marrow transplants of stem cells harvested from adult mice that were genetically engineered to glow green. Researchers were able to trace the origin of new blood vessels that formed in the animals' retinas back to the stem cells they had infused because the vessels glowed green.

"We were able to show that, essentially, the majority of the vessels being repaired in the eye were green," Scott said. "We could see entire green blood vessels, whole new capillary beds that were green."

The researchers also transplanted some mice with a single green stem cell.

"Everything that glowed green in those animals, therefore, came from a single cell," Scott said. "That was our formal proof that it was indeed a blood stem cell that was making these blood vessels."

Scott's UF collaborators included Dr. Maria Grant, Dr. W. Stratford May and Ammon Peck. The study was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Leukemia and Lymphoma Society of America.

The process by which blood stem cells form new vessels is likely to be very complex. Future research will focus on defining every step. Researchers also will seek ways to harness the body's ability to repair itself.

"We want to know what exactly recruits this activity from bone marrow," Scott said. "Does it happen normally or only in response to injury? With respect to diseases like diabetic retinopathy, we're trying to understand how these cells are recruited to the sites of injury in the eye so we could potentially someday block that activity and prevent diabetic retinopathy. Or perhaps we could promote [cell recruitment] and prevent other vascular diseases through a bone marrow transplant.

"Better yet, we're hoping we'll someday learn how to get your own stem cells to respond on their own and repair vascular damage, whether it's caused by a heart attack or the circulatory problems associated with diabetes," Scott said.

Donald Orlic, an associate investigator with the National Human Genome Research Institute at the National Institutes of Health, said the findings "provide a striking demonstration of the ability of adult bone marrow stem cells to generate new blood vessels in distant organs."

"This exciting advance in the field of regenerative medicine may ultimately enable us to understand the basis for building blood vessels in diseased tissues deprived of adequate oxygen," Orlic said. "Furthermore, based on these observations, we now know there is a population of stem cells in bone marrow that can produce either blood cells or blood vessels. This suggests that in the adult there are cells equivalent to the 'hemangioblasts' of the embryo, primitive cells that can differentiate into either blood or vascular cells."

Source: University of Florida