Preliminary Study Finds Stem Cells In Blood Restore Damaged Heart Muscle

While other researchers have shown that stem cells derived from bone marrow and umbilical cord blood can regenerate cardiac tissue, this study demonstrates that adult stem cells circulating in blood can also repair a heart.

In the study, published online in the current issue of the journal Circulation, the scientists found that human blood stem cells -- "master" cells that produce other types of body cells as needed -- regenerated heart muscle cells as well as artery tissue in mice whose hearts were injured.

"This takes us a big step ahead," says the lead author, Edward T. H. Yeh, M.D., professor and chair of M. D. Anderson's Department of Cardiology. "Taking stem cells from blood is a lot easier, and a lot less painful, than taking it from bone marrow.

"For patients, it would be as simple as donating blood," he says. "We would then isolate these potent cells and give them back to the patient where the damage has occurred."

While the researchers are cardiologists and cancer specialists, and are interested in treating heart failure that occurs in up to 10 percent of patients who use chemotherapy, they say such cell-based regeneration therapy could benefit patients who have had a heart attack or other injuries that have led to heart failure. "Such a therapy cannot bring back dead heart muscle, but it can help restore weakened hearts, no matter what the cause of the damage was," says Yeh.

The research also contributes more evidence to the idea that stem cells circulating in the blood can transform themselves into different organ systems as needed to repair injury -- a notion dubbed "stem cell plasticity" that is both revolutionary and controversial. The theory, pioneered by M. D. Anderson researchers Martin Körbling, M.D., and Zeev Estrov, M.D., upsets longstanding beliefs that different kinds of tissue have their own supply of stem cells to repair damage. If correct, however, stem cell plasticity could be used to repair, or even replace tissues and organs injured by cancer, say Körbling and Estrov, who are co-authors on this study.

To conduct the study, the researchers collected a supply of human stem cells from what is generally regarded as debris from the process of banking human red blood. (After blood is collected from volunteers, it is separated into white and red blood cells, and the white blood cells are usually thrown away.) The scientists collected white blood cells and then searched for those cells that express a protein (CD34+) that is known to be associated with stem cells. They then isolated cells with the CD34+ marker from the white cells.

To test whether peripheral blood stem cells could regenerate tissue, the research team used two groups of mice that were engineered not to have an immune system, so that they would not reject human cells. One group of mice was given an artificially induced heart attack, and then immediately treated with an injection of the human stem cells. The other mice, with healthy hearts, also received the stem cell therapy.

The researchers found that in mice with an injured heart, new cardiac muscle cells (myocytes) had developed at the edge of damaged tissue, and several layers of new blood vessel tissue (endothelial and smooth muscle cells) had also grown. Little evidence of such repair was found in the mice with healthy hearts, says Yeh.

"We've shown that CD34+-associated cells can actually transform into three different cells used by the heart, and that tissue damage is critical to this process," he says.

Several sources for regenerative stem cells have been suggested, such as bone marrow, cord blood and embryonic cells, but this study "demonstrates that adult blood stem cells may be an alternative to these other sources of cells for myocardial regeneration," says Yeh. "And blood is a readily available source of stem cells that does not require significant manipulation."

Yeh notes that no stem cell protocol has been approved in the United States to date, and that most human trials using stem cells (those derived from bone marrow) have taken place in Europe and South America. Still, Yeh says he hopes his research can advance in the near future.

The study was funded by M. D. Anderson.

Co-authors include Estrov, a professor of the Division of Bioimmunotherapy; Körbling, a professor in the Bone Marrow Transplantation Program; and Sui Zhang, M.D., Ph.D., all of M. D. Anderson. Also collaborating on the study were Henry D. Wu, M.D, and James T. Willerson, M.D., of The University of Texas Health Science Center at Houston. Yeh carries a joint appointment at The Health Science Center and the Texas Heart Institute.