Published online 29 May 2009 | Nature | doi:10.1038/news.2009.522


Early heart muscle cells identified

Mouse studies could one day aid human heart transplants.

Researchers may have isolated embryonic mouse cells that are committed to becoming cardiac myocytes, the type of heart muscle cells that are capable of coordinated contraction. Such cells could be a powerful tool in animal models of heart disease, and might pave the way for identifying the equivalent cells in humans.

"If the cells are what [the researchers] think they are, it will be a significant step forward," says Ulrich Martin, a stem-cell researcher at Hannover Medical School, Germany, who was not involved with the research. The results were presented this month at a meeting on regenerative medicine in Beijing.

Cells that develop down the wrong pathway could lead to arrhythmia, or an irregular heart rhythm.Wikimedia Commons / Stanwhit607

Previously, scientists had identified so-called multipotent secondary-heart-field (SHF) progenitors — those that can give rise to different major cell types in the mature heart, such as cardiac myocytes, smooth muscle cells and endothelial cells that form the interior surface of blood vessels. However, little is known about what drives these progenitor cells down one path instead of another. And that's not good for regenerative medicine, as transplanting SHF progenitor cells into a heart might mean they end up turning into a cell type other than heart muscle.

Ibrahim Domian, of Massachusetts General Hospital in Boston, and Kenneth Chien, of the hospital and the Harvard Stem Cell Institute, have been working on ways to label populations of cardiac progenitor cells in transgenic mice. At the Beijing meeting, Domian reported that they had isolated embryonic stem cells from those mice and identified different progenitor populations that express different sets of genes. One type of progenitor expressed the protein Islet-1, a marker of SHF progenitors; in culture, the cells divided for a few days before differentiating into mature cardiac muscles.

The researchers also found that cardiac myocetes derived from these progenitor cells contracted with a level of force — the defining characteristic of cardiac muscle — that was the same as neonatal cardiac myocytes. Domian declined to discuss details, stating that the results are under review at a journal.

"This is a very interesting study," says Martin. Progenitor cells that are committed to becoming cardiac muscles, but that can still reproduce, would allow researchers to expand them in culture before transplantation.

Domian and his colleagues are now trying to see if there are equivalent cardiomyocyte progenitors in humans, but these are more difficult to study because there are limited samples. So researchers such as Martin have turned instead to induced pluripotent stem (iPS) cells, which are artificially derived from cells that usually differentiate into only one type, but are then forced to express certain 'reprogramming factors' that allow them to develop into all cell types.


In other work reported at the Beijing meeting, Martin and his colleagues introduced some of those reprogramming factors into human umbilical-cord blood cells and generated iPS cells that are very similar to embryonic stem cells. When cultured in suspension, those cells formed the typical aggregates called embryonic bodies that contain cells from all three germ layers, a definitive feature of embryonic stem cells. One-fifth of the embryonic bodies were contracting clusters, and contained cells that looked and behaved like cardiac myocytes.

Martin and his team are now promoting and enriching particular heart-cell lineages that could be used as cellular transplants for treating heart disease. 

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