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Human Stem Cells Transformed Into Mouse Heart Cells

Researchers have transformed human adult bone marrow stem cells into mouse heart muscle cells that remained healthy and functioning in mice for more than two months.

The findings may eventually provide hope for millions suffering from disease-damaged hearts, University of Florida scientists say.

"Knowing that the cells are able to be transplanted successfully into the heart may one day enable the application of this stem cell population to human disease," said Barry Byrne, M.D., Ph.D., co-director of UF's Powell Gene Therapy Center and one of the authors of an article published last month in Circulation, a journal of the American Heart Association.

Unlike skeletal muscle, adult cardiac muscle damaged by deficient blood flow lacks the ability to regenerate, resulting in irreversible heart tissue death.

UF scientists found that within two weeks after human bone marrow stem cells were injected into the coronary arteries of a type of immunodeficient mice, the stem cells differentiated into heart muscle and adopted many of the characteristics of the surrounding tissue.

The study was conducted in an effort to expand knowledge about the transformational abilities of human bone marrow cells, but UF researchers say the technique may be able to be tested in people with heart damage within two to three years.

The findings advance prior studies -- which involved bone marrow stem cells from mice injected directly into the heart walls of the animals -- by using a purified form of human stem cells all of the same class delivered in a safer, more uniform manner via the circulatory system.

Using sophisticated testing methods, UF researchers verified that the transformed stem cells bore the same physical characteristics as mouse heart cells.

"We were able to examine the new cells in the heart tissue and see the characteristic patterns of protein expression in cardiac cells," said Byrne, an associate professor in the UF College of Medicine departments of pediatrics, and molecular genetics and microbiology.

Byrne conducted the study in conjunction with scientists from the Johns Hopkins School of Medicine and Baltimore-based Osiris Therapeutics. It was funded by the National Institute of Standards and Technology (NIST) and by Osiris.

"These findings provide a detailed snapshot of the regenerated stem cells' behavior in the heart tissue, far beyond patterns of gene expression," Byrne said.

For nearly 100 years, cardiovascular disease has been the No. 1 killer in the United States, accounting for more than 40 percent of all deaths. Nearly 62 million Americans have one or more types of the disease, according to the American Heart Association.

Stem cells are "master cells" that are able to develop into any of the cell types in the body. Because of their early stage of development, many scientists have focused on embryonic stem cells, derived from embryos created for fertility treatments.

Adult stem cells, such as those used in the latest UF study, are turning out to be much more versatile than had once been thought, and cells derived from bone marrow have been reported to be able to produce nerve, liver and even brain cells.

In the current study, a type of stem cells called human mesenchymal stem cells -- which give rise to skeletal muscle tissue -- that were derived from the bone marrow of four volunteers, differentiated into heart muscle cells called cardiomyocytes in mice that lacked the ability to mount an immune response against the human cells.

The stem cells were injected into the coronary arteries of the left ventricle, and a portion of them settled in the heart.

At various points over a two-month period, the heart tissue was analyzed to determine implantation and differentiation of the stem cells using marker genes and immunofluorescent staining for common cardiac proteins.

In 12 of 16 mice, implanted stem cells were found dispersed throughout the myocardium at four days. Over time, these cells began to take on the form and function of the surrounding cardiomyocytes, and after 14 days became indistinguishable from the rod-shaped heart muscle cells.

Byrne and other UF scientists are continuing the research and now are studying the ability of human bone marrow stem cells to regenerate heart muscle cells in animals with various types of heart muscle injury, such as cardiomyopathy.

In an effort to improve safety and effectiveness, they also are investigating an alternative method of delivering the stem cells to damaged heart tissue in conjunction with gene therapy vectors now used primarily to carry corrective genes.

[Contact: Paula Rausch]






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