Cardiac regeneration  pg. 3

Vanderbilt stem cell expert Antonis Hatzopoulos, Ph.D.  In the background, intravascular ultrasound images of the coronary artery, courtesy of Matthew O'Donnell, Ph.D., University of Washington College of Engineering.
The image was created by O’Donnell’s group at the University of Michigan Biomedical Engineering Department, in conjunction with EndoSonics, now Volcano Corporation.
Photo by Dean Dixon
A major push in the field is to find a stem cell source that is closer to the ultimate goal of generating new heart tissue.

Mesenchymal stem cells, found in the bone marrow and other adult tissues, are known to differentiate into a variety of different cell types in the lab, including fat, cartilage, bone, muscle and nerve cells.

“Mesenchymal cells are closer to becoming heart,” says Hatzopoulos, than are other types of stem cells in the bone marrow. This places them at an advantage, but they still require some additional “push” to enhance their therapeutic efficacy.

Super stem cells

At Vanderbilt, Pampee Young, M.D., Ph.D., assistant professor of Pathology and Medicine, and her colleagues are working to identify that push. From a mouse strain that naturally exhibits a high level of regenerative capacity, Young has isolated “super” mesenchymal stem cells.

When injected into mice that have had a heart attack, they secrete factors that increase the proliferation of cardiomyocytes. Their ability to improve heart function after myocardial infarction exceeds that of injections of “normal” mesenchymal stem cells.

One factor that may play a role in their enhanced regenerative capacity is a signaling pathway known to set up the vertebrate body plan early in development, the Wnt pathway.

“We have identified a striking downregulation of the Wnt pathway in the ‘super’ mesenchymal stem cells,” Young says.

Downregulation enhanced mesenchymal stem cell proliferation, she adds, so “modulating the activity in this pathway… may be an excellent future target for cell-based therapies for myocardial injuries.”

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