Researchers have integrated heart cells grown from human embryonic stem cells into a host heart

Researchers at the Technion-Israel Institute of Technology and Rambam Medical Center have demonstrated that heart cells grown from human embryonic stem cells can integrate into the host heart and help regulate its activity, becoming in effect a biological pacemaker.

This breakthrough may lead to the development of a biological pacemaker and to using heart cells to repair heart tissue destroyed by heart attacks. The study is published in the September 26, 2004 issue of Nature Biotechnology.

"This is extremely important research," says Dr. David Gutterman, professor of medicine and physiology at the Medical College of Wisconsin and associate director of its Cardiovascular Research Center. "This could lead to a replacement of the mechanical pacemaker, which requires surgery to replace the battery every few years. We could also replace beating cells in patients who have had heart attacks. Dr. Gepstein is on the forefront of heart rhythm research."

"This is an important proof of concept that heart cells can have the ability to integrate within existing cells," says lead researcher Dr. Lior Gepstein of the Technion Faculty of Medicine.

Dr. Gepstein and his colleagues were the first to generate human heart tissue in the laboratory, which could be used for testing and creating new drugs for genetic studies, for tissue engineering and for studying the effects of various stresses on the heart. The team, however, wanted to test if the cells could function and integrate within a live host body.

They placed beating human heart cells, derived from the stem cell line, onto rat heart tissue. By recording the electrical activity from both tissues, they were able to show that the two tissues integrated electrically to form a single functional unit in which rat and human cells were beating in perfect synchronicity.

This concept was then tested in living animals with slow heart rates. The team transplanted human pacemaker cells derived from the embryonic stem cell line into the animals’ hearts. Using specialized electrical mapping equipment developed by the Technion researchers, they were able to pinpoint where the heart rate originated within the living animal, which turned out to be at the immediate region containing the transplant. This demonstrated that the implanted cells had integrated into the host heart, and by regulating its pace were behaving like a biological pacemaker.

Technion scientists are widely recognized as pioneers in stem cell research. Dr. Joseph Itskovitz-Eldor was among the team that first discovered in 1998 the potential of stem cells to form any kind of tissue. Technion researchers have since grown heart tissue, blood vessels, and human insulin-secreting cells from embryonic stem cells. And scientists at the Technion are now able to grow an infinite number of cells without a feeder layer, making these cells appropriate for eventual human transplantation.

Heart disease is the leading cause of death in the U.S. Abnormally slow heart rate develops in older patients, who can only survive with an electronic pacemaker. During heart attacks, tissue is destroyed when blood is temporarily cut off to a section of the heart, and this tissue can never be repaired. Cell therapy has the potential to treat these currently nearly untreatable diseases.

Dr. Gepstein says that while obstacles remain before the research leads to cell therapy, these groundbreaking results demonstrate that this type of treatment will be possible.

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