Researchers isolate a master heart cell

A team of Harvard scientists announced yesterday that it has discovered a single kind of cell that builds the three main types of heart tissue, an advance that boosts the prospects of using cells to treat heart disease, the nation's top killer.

The team identified the heart cell in mice, and proved that it develops into the muscle cells that power the heart, the cells that make up blood vessels, and the smooth muscle cells that allow the vessels to expand and contract.

If the human equivalent of the new cells is found, it could be given to patients to rebuild heart tissue that cannot be repaired today. The work could also give biologists new tools to look for heart drugs.

There has been a rush of work in recent years to develop therapies that inject cells capable of repairing patients' damaged heart muscle. But the field has been hampered because biologists have not known what type of cell to use. Researchers around the world have launched clinical trials, but the trials have used blood cells, not heart cells, and the results have been modest, at best.

The research identifies, for the first time, a kind of master heart cell, similar to a stem cell, with a proven ability to build a wide range of heart tissues. The scientists cautioned that important obstacles remain before cell therapies based on the research can be tested in humans.

Other researchers said the work, combined with new results from two other research teams, will force a fundamental shift in thinking about how the heart develops.

"This is an important milestone," said Dr. Deepak Srivastava, who was not involved in the work and who is director of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. "As one tries to use cells for therapeutic applications, it is much easier if one is able to use a single pool [of cells] that can turn into all the component parts."

Unlike some organs of the body, the heart has a very limited ability to repair itself, so doctors have found it difficult to reverse the cardiac effects of disease or congenital defects. With better surgical techniques and new drugs, heart medicine has scored major victories, but still nearly 1 million Americans every year die of heart disease.

Recently, cardiac specialists have begun to talk more seriously about the idea of substantially rebuilding damaged hearts. One strategy has been to better understand how the body builds a heart in the first place, with the hope of finding cells that retain this ability long after the heart has been formed.

It is not known whether the new cells remain in the adult heart, according to Dr. Kenneth R. Chien, who led the work and is director of the Cardiovascular Research Center at Massachusetts General Hospital and of the cardiovascular disease program at the Harvard Stem Cell Institute. Even if the cells do not remain in the adult heart, he said, it may be possible to create them using human embryonic stem cells, which have the ability to become any cell in the body.

The research, published online yesterday by the journal Cell, follows work announced last year, in which Chien identified a heart cell that can create new heart muscle cells. The new work appears to have identified what is effectively the father of that cell -- a more versatile cell that can create muscle, as well as the two other main types of heart tissue.

In the past, Chien said, biologists suspected that the many tissue types in the heart were formed by many different "progenitor cells." The new research suggests that there may be just one type of cell that is capable of producing all the tissues. (The scientists have not shown that the cells can make every specialized cell in the heart, just the main types.)

This theory is supported by two other new papers. One, also published online yesterday by the journal Cell, identifies a different heart cell that is able to produce two of the three major types of tissue in the heart. This cell may represent a later, more specialized version of the cell found by Chien, or it may be unrelated, according to that project's senior scientist, Dr. Stuart H. Orkin . Orkin is a scientist at Children's Hospital Boston who holds positions with Harvard Medical School, the Howard Hughes Medical Institute, and the Harvard Stem Cell Institute. The other paper supporting the idea appears in the November issue of Developmental Cell, a sister publication of Cell.

Chien said his team is working on ways to translate the research into potential therapies for people.

One of the more important initiatives now, he said, is to attempt to coax human embryonic stem cells to become a heart cell like the one he found in mice. Embryonic stem cells have the ability to form any tissue in the body, but they need specific chemical cues to become particular types of cells. Chien hopes to discover how to force embryonic stem cells to become the master cell he has found, and also to become the more specialized cells of the heart.

If this can be done, it could in theory give doctors a way to replace damaged tissue in a heart. Human embryonic stem cells cannot be directly given to a patient, because they would form cancerous tumors. But more specialized cells might be able to regenerate the heart without the risk of cancer. More immediately, having these more specialized cells would give researchers a new way to test drugs, and to study how the heart develops, perhaps leading to new insights.

Chien's team has already begun working with human embryonic stem cells, and the initial data, he said, have been encouraging.

Gareth Cook can be reached at cook@globe.com.