Cells morphed to muscle may aid in heart failure therapy

Tissue from the hearts of mice morphed into muscle cells with the ability to beat and form electrical connections, in an experiment that may lead to new therapy for more than 5 million Americans with heart failure.

Connective-tissue cells called fibroblasts makes up about half the cells in the heart. Researchers led by Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease in San Francisco, said they used a trial-and-error process to identify three genes able to turn fibroblasts into heart muscle.

The technique may enter clinical trials in as little as five years to test whether damaged areas of patients' hearts can regenerate, Srivastava said. Heart failure has no cure and will cost the health care system $39 billion this year, according to the American Heart Association.

"It points to a whole new way of potentially doing therapy," said Chad Cowan, an assistant professor in the department of stem cell and regenerative biology at Harvard University. "This gives you the idea that you can take those fibroblasts, re-educate them to become heart muscle and thereby repair someone's heart."

The research, published yesterday in the journal Cell, follows work by Shinya Yamanaka, of Kyoto University in Japan, who in 2007 identified genes that transformed skin cells into the equivalent of embryonic stem cells.

After a heart attack, the blood supply to the organ is cut off, leaving sections without the oxygen they need. Cells in the oxygen-starved areas die, form scar tissue and no longer contract properly, impairing the heart's pumping. Patients with this kind of damage, known as heart failure, can become exhausted by walking or climbing stairs.

Damaged parts of the heart can't regenerate because they have no ability to make new muscle cells, Srivastava said in a telephone interview. Researchers have hoped that stem cells might regrow heart muscle.

Efforts to transplant adult stem cells into patients' hearts have led to modest improvements at best because the stem cells failed to form new heart muscle, Srivastava said. His technique may provide an alternative to stem-cell transplants by tapping into and converting a supply of cells already in the heart.

Srivastava's research is the most advanced example so far of a new approach to altering the function and destiny of cells, a process known as directed differentiation. Instead of getting cells to revert to an immature stem-cell state, then converting them to a particular cell type, scientists try to turn one kind of mature cell directly into another.