September 10, 2007

Stem Cell Treatment Repairs Damaged Rat Hearts

Yellow areas among many green areas Human-derived heart muscle cells (yellow) thrive alongside normal heart muscle cells (green) in a rat heart.Charles Murry, University of Washington

Researchers have developed a procedure for repairing damaged rat hearts by using cells generated in a dish from human embryonic stem cells. The accomplishment brings scientists a step closer to a treatment for people who have had heart attacks.

A type of cell naturally found in embryos, called a stem cell, has the potential to become almost any cell or tissue in the body. This ability has led many scientists to believe that these cells may prove useful for replacing damaged cells and tissue. Over the past few years, researchers have made significant progress in learning how to coax embryonic stem cells to become other types of tissue in the laboratory.

Dr. Chuck Murry of the University of Washington led a research team trying to develop a procedure for repairing damaged hearts. Their work was funded by NIH's National Heart, Lung and Blood Institute (NHLBI), National Institute of General Medical Sciences (NIGMS) and National Institute of Biomedical Imaging and Bioengineering (NIBIB), along with the Geron Corporation.

Previous research showed that human embryonic stem cells could be transformed into heart muscle cells in the laboratory and then grafted into the rat heart. However, repairing a damaged heart poses a considerably greater challenge. The researchers estimated it would take about a thousand times more cells to actually repair a damaged heart. They realized they faced an even greater challenge after testing the cells in rats whose hearts had been injured. In contrast to the 90% success rate they achieved in uninjured rat hearts, only 18% of the damaged rat hearts incorporated the human cells.

As they explained in the science journal Nature Biotechnology, published online on August 26, 2007, the researchers first developed a procedure for making a preparation with more heart muscle cells. Then, through a process of trial and error, they developed a complicated mixture of chemicals, which they call a "prosurvival cocktail," to protect the cells from dying once inside the rat's body.

All of the rats that received the improved heart muscle cell preparation, along with the prosurvival cocktail, had implanted cells in their damaged hearts after 4 weeks. In almost all cases, the grafts formed new heart muscle. The implanted cells looked smaller and less mature, but seemed to be incorporated into the organization of the heart tissue. The researchers didn't detect the cells in any other rat organs, nor did they find evidence for tumors or other inappropriate tissue formation.

When they tested for heart function, the researchers found that their treatment thickened the damaged walls of the rats' hearts and improved their ability to contract.

This research shows that heart muscle cells grown in the laboratory from human embryonic stem cells can improve both the structure and the function of damaged rat hearts. The next step, the researchers say, is to conduct experiments in larger animals, such as pigs or sheep. While there's still a long research road ahead, human heart attacks may one day prove to respond to treatment with a similar preparation.

— by Harrison Wein, Ph.D.

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