Repairing Hearts with Bone Marrow

Applied Genetics News,  April, 2001  

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New research shows it is possible to rebuild heart attack-damaged hearts with adult stem cells from bone marrow. Scientists at the National Institutes of Health (NIH) and New York Medical College (Valhalla, NY), demonstrated for the first time that adult stem cells isolated from mouse bone marrow could become functioning heart muscle cells when injected into a damaged mouse heart. The new cells at least partially restore the heart's ability to pump blood.

The research team was led by Donald Orlic, Ph.D., a staff scientist in the genetics and molecular biology branch of the Division of Intramural Research at the National Human Genome Research Institute (NHGRI), and Piero Anversa, professor of Medicine and director of the Cardiovascular Research Institute at New York Medical. They report their results in the April 4, 2001 issue of Nature.

"The apparent ability of stem cells in the bone marrow of adult animals to rebuild the heart reveals nature's remarkably flexible response to disease," comments Francis Collins, NHGRI Director.

In their search for a way to reverse heart attack damage, the team began by isolating bone marrow stem cells from male mice. The isolated stem cells carried a newly inserted gene that produces green fluorescent protein (GFP), a marker that enabled the researchers to identify the transplanted cells. In addition, the researchers decided to transplant stem cells from male mice into female hearts so they could show definitively that any new heart muscle had come from donor cells.

The researchers then gave the female mice a heart attack by tying a suture around a coronary artery commonly blocked in human disease. A short time later, they injected the labeled stem cells into the heart muscle next to the damaged tissue. Over the next 7 to 11 days, the stem cells began to multiply and transform themselves into heart muscle cells and migrated into the damaged area. After an average of 9 days, the newly formed heart muscle cells occupied 68% of the damaged portion of the heart. In addition, the stem cells also began producing smooth muscle cells and endothelial cells that organized themselves into new blood vessels.

"Initially, I thought if there was a little regeneration, some heart muscle cells forming, then that would be considered successful," NHGRI's Orlic says. "Instead, our expectations were far exceeded in terms of seeing not just heart muscle cells, but blood vessels and functional measurements showing that the repair actually improved cardiac output."

The treatment only worked in 12 of 30 mice, approximately 40%. That may be due to the difficulty of injecting the stem cells into a heart that beats on the average of 600 times per minute. Nevertheless, New York Medical College's Anversa predicts that if follow-up studies go well, clinical trials in human patients could begin in three years.

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