Master Stem Cell for Human Heart Identified

WEDNESDAY July 1, 2009 -- For the first time, researchers have identified a single "master" stem cell in humans that is capable of differentiating into all three major cell types that make up the human heart.

"This is a very simple but very important and fundamental finding, and that is understanding how the human heart is built, how it is made, what are the progenitor cells which give rise to the human heart," said Dr. Kenneth Chien, head of the Harvard Stem Cell Institute's cardiovascular disease program and senior author of a paper in the July 2 issue of Nature.

"This means we are in a new era where we can envision entirely human-based models of cardiovascular disease," added Chien, who is also director of the Massachusetts General Hospital Cardiovascular Research Center.

Because this is a first, there could be enormous implications for further research into the human heart and, eventually, into repair and regeneration of the organ in people who have had heart attacks or have heart failure or congenital heart defects.

Understanding the mechanisms of the human heart might also help in the development of drugs with fewer heart-related side effects as well as allow better monitoring of drugs already available. Chien, who spoke to journalists in teleconference Wednesday, pointed out that many widely used and valuable drugs, such as Herceptin (for cancer) and Avandia (for diabetes), have heart-related side effects. The painkiller Vioxx was withdrawn from the market after widely publicized side effects were noted.

The breakthrough research "offers more understanding of how to model the development of the human heart, and, by understanding that, we might be able to understand what goes wrong," said Paul Sanberg, a stem cell expert and director of the University of South Florida Center for Aging and Brain Repair in Tampa. "One day there may even be the potential for stem cell therapy."

Although the genesis of the heart has been studied extensively in organisms including zebra fish, flies and mice, much less is known about what happens in the human heart, Chien said.

And while stem cells have been used to treat people after a heart attack, for instance, cells that are used are not from the heart and it's not yet clear how effective the approach really is.

Chien and his team used antibodies directed against islet progenitor cells in human fetal hearts to identify the presence of the cells. They then purified the cells, cloned them and tracked their journey from single stem cell to the three major lineages of heart cells -- smooth muscle, cardiomyocyte muscle and endothelial cells.

Chien said that he thought it would be "entirely unlikely" that scientists would be able to use these cells to "grow" a whole heart.

Instead, the key seems to be in identifying intermediary points and pathways by which the cells branch off into very specific types of cells and subsets of the major cells so they could be directed to these specific destinations.

"This sets up a system where we can now use scientific tools to rigorously identify the pathways that would drive the cell to become the cell of interest and not become the other cell of interest, and to test each rigorously in animal models as to which one would have a therapeutic effect," Chien said.

The researchers suspect that defects in the decisions of these stem cells could be responsible for various types of congenital heart disease.

But there is a danger in using embryonic stem cells in humans, according to Dr. Darwin J. Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White. And that is the potential for the cells to form tumors down the line.

"How can you be sure that a few cells that are left aren't immortal and tumorgenic?" he asked.

But Chien said he thought both embryonic stem cells and induced pluripotent cells, which are coaxed from adult cells, both have potential.

More information

The U.S. National Institutes of Health have more on stem cells.

Posted: July 2009


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