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Bone Marrow Stem Cells Heal the Heart
  
By Nancy Touchette

In February, a teenager in Michigan received injections of stem cells from his own bone marrow to repair a damaged heart. The boy had suffered a massive heart attack after being accidentally shot in the chest with a nail from a nail gun. The first choice of treatment was a heart transplant, but no donor hearts were available. Instead, doctors at Beaumont Hospital in Royal Oak, Michigan, tried a novel treatment using the 16-year-old’s stem cells.

The patient was first treated with a drug that stimulates the production of bone marrow stem cells and their release into the blood stream. Stem cells were then collected and injected into his aorta. So far, ten percent of his heart has regained function, and doctors are cautiously optimistic for greater gains.

This is an example of promising experimental therapies involving stem cells from bone marrow. Until just a few years ago, conventional wisdom held that only embryonic stem cells could turn into any cell in the body. But that thinking began to change as studies showed that stem cells from bone marrow could become heart, muscle, nerve, or liver cells.

Doctors determine area of patient's heart (left) in which to inject bone marrow stem cells (right).

Now, the results of clinical trials conducted in Britain, Germany and Brazil show that heart patients injected with their own bone marrow cells benefit from the treatment.

In the British study, fourteen patients benefited from bone-marrow injections following heart attacks. The injections, into the scar tissue of their hearts, led to improvements in heart contraction within weeks, and the effects have persisted for more than ten months.

In the Brazilian study, fourteen patients in the late stages of heart disease improved four months after being injected with their own bone marrow cells. German researchers also reported striking improvements in five out of six heart attack patients three to nine months after receiving bone marrow cell transplants.

Bone marrow is a mixture of many cell types, including stem cells, progenitor cells, and mature blood cells. The next step, say researchers, is to identify the specific cell types that elicit the greatest response.

“Now we are in a race to find the best conditions to mobilize the bone marrow cells and make them differentiate into different types of tissues,” says Manuel Galiñanes of the University of Leicester in England, who led the British study. “We don’t know yet what cell is the one that is going to regenerate the whole tissue.”

The researchers do not yet know whether the patients improve because new heart muscle cells or new blood vessels have formed, but they suspect it may be a combination of both.

Despite these encouraging results, many researchers have expressed concerns about the treatments, pointing to the recent discovery that stem cells from bone marrow may fuse with other cells. This fusion could produce unstable cells that might trigger disease, according to some researchers.

“The cell fusion approach is not ready for the clinic,” says David Russell of the University of Washington in Seattle, who studies bone marrow stem cells in mice. “We need to show that this type of procedure is safe.“

Russell points out that bone marrow stem cells fuse with liver cells to produce hybrid cells that contain abnormal numbers of chromosomes.

“We need to show that these cells are genetically stable and will not gain or lose chromosomes and form tumors,” he says. “It’s important to know this before we talk about treating patients.”

Hope for Diabetes

Heart patients are not the only ones who may benefit from bone marrow stem cell therapy. Mehboob A. Hussain of New York University in New York finds that bone marrow stem cells can become pancreas cells that produce insulin, in mice. The process occurs without a fusion between the two cell types.

The finding could help people with type 1 diabetes, an autoimmune disease in which the insulin-producing islet cells of the pancreas are destroyed by a person’s own immune system. People with type 1 diabetes do not produce insulin and are not able to metabolize glucose. Hussain plans to extend his studies to cultured human cells before the procedure is tested in humans.

However, Galinañes says the clinical studies should not stop while researchers try to figure out the underlying mechanisms by which bone marrow cells become heart cells.

“It is vital that we understand the mechanism,” says Galinañes. “But the reality is that our findings are already showing a benefit to people who are desperately ill. Both types of research should proceed and grow together.”

The uncertainty over how one cell type changes to another has prompted at least one prominent researcher in the field to pursue a different approach.

Now, instead of using bone marrow stem cells to treat heart disease, Piero Anversa, of the New York Medical College in Valhalla, New York, is searching for primitive cells that reside in the heart and normally replace damaged heart cells.

“We are trying to move away from these complexities by identifying resident primitive cells that are already programmed to become heart cells,” says Anversa, who was the first to show that bone marrow stem cells could replace damaged heart cells in mice.

“If we use bone marrow cells, we are asking a cell that is used to making blood to switch and now make muscle,” he explains. “The cell has to reprogram itself.”

Once these primitive heart cells are identified, Anversa says, it may be easier to devise ways to replace damaged heart tissue because these cells are already programmed to generate new heart cells. He adds that understanding the process by which heart cells regenerate may lead to new strategies to slow down aging.

See related GNN articles
»Cultured Eggs Could Defuse Stem Cell Politics
»Stem Cell Therapies: Time to Step Back or Forge Ahead?
»Stem Cell Alert: Laws and Players

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Vassilopoulos, G. et al. Transplanted bone marrow regenerates liver by cell fusion. Nature 422, 901-904 (2003).
 
Wang, X. et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422, 897-901 (2003).
 
Ianus, A. et al. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J. Clin. Invest. 111, 843-850 (2003).
 
Perin, E.C. et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, published online May 13, 2003.
 
Stamm, C. et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361, 45-46 (2003).
 
Galinanes, M. et al. Safety and efficacy of transplantation of autologous bone marrow into scarred myocardium for the enhancement of cardiac function in man. Circulation 106, published online October 15, 2002. supplement II: II-463.
 

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