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Master cell could mend a broken heart

November 22, 2006 By Narelle Towie This article courtesy of Nature News.

Stem-cell research uncovers the heart's foundations.

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Researchers have uncovered a 'master' stem cell responsible for producing all the major tissues of the heart. The surprising finding brings fresh hope to the idea of using stem cells to repair heart damage.

Two independent teams in the United States used genetic mapping techniques to search for muscle-building stem cells in embryonic mouse hearts. Together they uncovered two cell types fundamental to the construction of the heart, one of which accounts for all three major tissue types and, scientists suspect, probably gives rise to the other.

The results overthrow the previous theory that different source cells would be needed for each muscle type. And that spells good news for future research. Fixing the damage done to heart cells by a heart attack, for example, should be much easier if only a single master stem cell needs to be used.

"We are going to take the tools that we have learned from embryonic stem cells in the mouse and work out how to use them in humans," says Kenneth Chien of Harvard Medical School, who led one of the two teams. "We believe we could take this cell and engineer tissue for specific components of the heart," he says.

But the idea of using these stem cells to repair the damage done by a heart attack is still a long way off. "The public should not be misled," says Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. "It's an important leap forward but there are still many technical hurdles."

Master and parent

Chien's team, which reports its results in Cell1, traced cells expressing the islet-1 gene, which has previously been linked with cells in cardiac muscle (see 'Heart-renewing' cells discovered). The researchers used markers placed in the gene to trace which muscles the cells containing it developed into. Surprisingly, they found that these cells produced all the major heart muscle types.

A second group, led by Stuart Orkin, also of Harvard Medical School, traced cells containing the Nkx2.5 gene, which is known as tinman in fruitflies because of its ability to render them heartless when turned off. Cells with this gene made two types of heart muscle, in a part of the heart that develops first, the researchers report, also in Cell2. The researchers suspect, but have yet to prove, that the cells containing islet-1 are the parent of these cells.

"It now appears that cardiac cells develop in the same way that blood cells do, with a master stem cell giving rise to the entire range of cells," says Chien.

The next step is to work out how the master cells decide which type of heart muscle to develop into. And the researchers also need to develop ways to make the cells reproduce in the lab.

Human trials are already taking place in which stem cells obtained from bone marrow are injected directly into the hearts of patients (see ' Trial set to test how stem cells heal a broken heart'). But the procedure is controversial it is unclear whether the stem cells are actually transforming into heart muscle cells. The stem cells found by Chien's group are much more specific to the heart, and so should be more effective at repairing damaged tissue. But they are also much more difficult to obtain.

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References

  1. Moreti A., et al. Cell, doi:10.1016/j.cell.2006.10.029 (2006).
  2. Wu S. M., et al. Cell, doi:10.1016/j.cell.2006.10.028 (2006).

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