Tracking the Uncertain Science of Growing Heart Cells

By NICHOLAS WADE

Published: March 14, 2005

In April 2001, researchers from the New York Medical College and the National Institutes of Health announced electrifying news for heart surgeons and their patients: stem cells from bone marrow, injected into the damaged hearts of mice, had morphed into the special cardiac muscle cells that the body cannot replace after a heart attack.

The researchers held out the hope that the procedure could be applied to people, too. The findings underlined a basic premise of stem cell therapy, that it will work before the cells and their elaborate control systems are fully understood - just put stem cells in the right place in the body, and they will do the rest.

But four years later, the treatment has yet to demonstrate whether it will fulfill its promise. And it has touched off a sharp difference of views among clinical doctors as to whether the therapy is ready to be taken to people.

Ten human trials of the marrow-to-heart approach have been completed in clinics around the world, all but one with positive results. But the overall degree of improvement in the patients' heart function has been modest. At the same time, the original research that provided the rationale for many of the trials has come under severe criticism from scientists who have tried without success to reproduce it.

The approach, if it works, would be a leading example of regenerative medicine, the idea that the best way to repair the body is not with strong drugs or the surgeon's scalpel but with the body's own system of cells and signaling molecules. Regenerative medicine should work, in principle, on the host of diseases that result as aging organs and tissues fail to maintain the vigor of youth.

The difficulties of the marrow-to-heart therapy do not dash the hopes for regenerative medicine or imply failure for the stem cell research financing set up by states like California and New Jersey. But they do suggest that successful stem cell treatments, whether with adult cells or ones derived from embryos, may require many years to come to fruition.

The bone marrow stem cell technique, devised by Dr. Donald Orlic of the National Institutes of Health and Dr. Piero Anversa of New York Medical College in Valhalla, N.Y., was taken up with such alacrity because it promised to address a desperate medical need and seemed reasonably safe, given that patients were to be injected with their own cells. Patients are now being recruited for at least two trials in the United States, one at the Texas Heart Institute in Houston and a second at the Caritas St. Elizabeth's Medical Center in Boston and two other sites.

The Houston trial, led by Dr. James T. Willerson and Dr. Emerson C. Perin, follows from a test in Dr. Perin's native Brazil. Though Brazilian regulators would allow only the sickest patients to be enrolled, Dr. Perin said, there was "significant evidence" that the treatment worked. Before receiving injections of their bone marrow stem cells, most of the patients were bedridden or too sick to walk without effort. But after treatment, he said, "some patients were jogging on the beach, one climbed eight flights of stairs, and one, who had gone home to live with his mother, reopened his business."

On the strength of these results, the Food and Drug Administration allowed the Texas Heart Institute to start recruiting patients for a similar trial. So far 13 patients with end-stage coronary disease have been treated, and all are doing well. "We are thrilled by what we have seen," Dr. Willerson said of the two trials.

At the St. Elizabeth's Medical Center, Dr. Douglas W. Losordo has started recruiting patients and is also impressed with the results so far.

"There are dramatic examples of patients' going from being bedbound to living normal lives," Dr. Losordo said. Although the study is blind, meaning he does not know which patients were treated and which are serving as controls, the group as a whole is doing better. One patient who has left the study - the rules allow patients showing no response to be withdrawn after six months - turned out to be in the untreated group.