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Stem Cells Yield Promising Results March 31, 2001 - The basis of a possible revolution in treating heart attack patients has been laid by three reports of using stem cells from bone marrow to repair heart tissue in animals. In one of the studies, apparently functional heart tissue was regenerated from the injected cells, the first such success in some two decades of effort. In another, the stem cells morphed into new blood vessels that rescued the heart cells around the damaged area from their usual course of overgrowth and death. In the third, stem cells were used to strengthen pig hearts. The three groups of researchers, based at Columbia University, New York Medical College in Valhalla, N.Y., the National Institutes of Health, and Osiris Therapeutics of Baltimore, said they were a year or more away from testing their animal techniques in people. Still, heart disease experts believe the stem cell work is highly promising. "The health care industry would be revolutionized if the treatment of heart failure could be moved from organ transplants down to cell transplants," said Dr. Mark Sussman, a heart researcher at the Children's Hospital and Research Foundation in Cincinnati. The new research opened "some very exciting doors," Dr. Sussman said, but required considerable further work to make sure it was as promising as it seemed. Dr. Eugene Braunwald of Harvard, who is the author of a leading textbook of cardiology, said the idea of putting stem cells into the heart to grow new heart muscle cells was "a very interesting approach." If their animal techniques work the same way in people, the researchers say, people suffering a heart attack would be treated by having cells extracted from their bone marrow. The cells would be sorted and amplified, then injected either directly into the heart, or maybe just into the bloodstream, from which they would home in on damaged heart tissue and on the enlarged heart muscle cells that soon grow around it. It may even prove possible, though this concept has not yet been tested, to do no more than inject a heart attack patient with a cytokine, a natural protein that stimulates the bone marrow's stem cells to proliferate. The cells would home in on damaged heart tissue, and repair it. Biologists say it is too early to know if the blood-forming stem cells of the bone marrow are also the heart's own stem cells, which researchers have been seeking in vain for years, or if their remarkable ability to repair the heart is just a general property of stem cells. Stem cells are unspecialized cells that can turn into the mature cells of the body while replenishing their own numbers so as to remain a constant source of new cells. The cells involved in the new reports are called adult stem cells, and differ from the controversial embryonic stem cells that generate the fetus and adult organism. The new results all depend on the recent finding that the stem cells of the bone marrow are far more versatile than supposed and can generate other tissues besides the red and white blood cells, their best-known function. It seems that the cells are a kind of universal clay, so responsive to local cues that if placed in the heart they will develop into heart tissue instead of blood cells. In one of the new reports, published in this month's Nature Medicine, Dr. Silviu Itescu and colleagues at Columbia University say they isolated a special kind of stem cell from human bone marrow. The cells, which they call angioblasts, are a subset of the blood-forming stem cells that make the red and white blood cells. Angioblasts generate the cells of the fine blood vessels. Although their existence had been inferred, they had not been isolated before, Dr. Itescu said. After a heart attack, caused by blockage of one of the heart's own arteries, the muscle cells that were deprived of oxygen die off and the cells around them grow four or five times larger to compensate for the damaged tissue. That is why most people survive a heart attack. But the overgrown cells themselves start to die after a time, and are replaced by scar tissue. The heart then starts to fail. Dr. Itescu said that his team thought the overgrown muscle cells might be dying for lack of an adequate blood supply, a point that could be proved if the cells could be rescued with a new blood supply. This was their rationale for learning how to isolate the angioblast cells. They then injected human angio- blasts into rats in which heart attacks had been induced by tying off a coronary artery. For reasons not yet understood, stem cells are much better tolerated by the immune system than other foreign cells. Injected into the rats' bloodstream, the human angioblasts homed in on the damaged heart tissue. Dr. Itescu said he had identified the signaling chemical emitted by the damaged heart cells, but declined to name it because he has not yet published his description of the work. The human angioblasts generated blood vessels within the damaged rat hearts and prevented the overgrown heart muscle cells from dying. The left ventricle's efficiency plunges after a heart attack, but in the treated rats it recovered by 30 percent 15 weeks after treatment, in step with the growth of new blood vessels. Dr. Itescu said he hoped that clinical trials would begin in about a year, after he had done more rat experiments to define the safety and timing of a treatment protocol. In a commentary, Dr. Nadia Rosenthal, a heart researcher at Massachusetts General Hospital, called the Itescu team's success at growing new blood vessels a "remarkable accomplishment." The second stem cell article, to be published in next week's Nature, was written by Dr. Piero Anversa of the New York Medical College in Valhalla and Dr. Donald Orlic of the National Institutes of Health and their colleagues. The Orlic-Anversa team purified cells from a donor mouse's bone marrow so as to isolate the most primitive stem cells and exclude those that had already taken the first steps toward becoming blood cells. The primitive stem cells were then injected directly into the hearts of other mice that had been given heart attacks by tying off an artery. The researchers found that the stem cells generated new heart tissue by maturing into different cells, including heart muscle cells, the smooth muscle cells of artery walls, and the cells that line the blood vessel walls. The mice's left ventricle efficiency was about 40 percent greater than that of untreated mice. This is the first time, Dr. Orlic said, that new heart tissue has been generated from injected cells. He and Dr. Anversa had expected to see just a few new heart muscle cells, and had gone to great trouble to label the donor cells with a fluorescent green protein so as to be able to tell them apart from the recipient's heart cells. "We never dreamed the cells could do this," Dr. Orlic said of the new heart tissue. Dr. Ronald McKay, an expert on neural stem cells at the National Institutes of Health and a coauthor of the Orlic-Anversa study, was also surprised by the new tissue formation. "No one has ever seen this kind of thing before — complete regeneration right across the graft site," Dr. McKay said. Dr. Orlic and Dr. Anversa believe the new tissue is functional because the mouse hearts improved and the new cells produced a special protein typical of heart cells that have formed a connective network so as to beat in unison. Dr. Sussman said this was good but not conclusive evidence that the stem cells can make working heart tissue. Still, Dr. Sussman wrote in a commentary in Nature, "The implications are profound: damage to the heart muscle after a heart attack might be reparable with specific bone marrow cells." In a third experiment, described this month at a meeting at the Cold Spring Harbor Laboratory on Long Island, Dr. Robert Deans of Osiris Therapeutics said he had improved heart function in pigs by injecting stem cells into the region of a heart attack. The pig is large enough that the improvement in its heart function can be measured more precisely than in rodents. Dr. Deans used a second kind of stem cell found in the bone narrow, known as a mesenchymal stem cell. The cells usually mature into bone, cartilage and fat cells. Injected into the pigs' hearts, they developed into heart muscle cells. Dr. Deans said he hoped to begin a clinical trial of the technique in a year, probably on patients awaiting heart transplants so that the effect of implanted cells could be precisely measured after the old heart was removed. Researchers have been trying for years to repair hearts by injecting different kinds of cells into them. Their persistent lack of success, Dr. Sussman said, may make others wary of the new claims at first. But the present options for treating heart failure are not so perfect: drugs to keep the heart limping along for some years and a transplant when it finally fails. "So it would be beautiful and also a phenomenal saving in economic terms and for people's quality of life if you could figure out a way to repair the existing heart," Dr. Sussman said. "I think this therapeutic approach, if it becomes viable, gives us an entirely new way of treating heart failure that did not exist before." By NICHOLAS WADE Copyright 2001 The New York Times Company http://www.nytimes.com/2001/03/31/health/31CELL.html?pagewanted=print janet paterson, an akinetic rigid subtype, albeit perky, parky PD: 54/41/37 CD: 54/44/43 TEL: 613 256 8340 EMAIL: [log in to unmask] "A New Voice" home page: http://www.geocities.com/janet313/ . "New Voice News" latest posts: http://groups.yahoo.com/group/nvnNET/ . ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn