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The newspaper of The Johns Hopkins University December 20, 2004 | Vol. 34 No. 16
JHU Scientists Develop Method to Replicate Stem Cells from the Heart

By David March
Johns Hopkins Medicine

In human and animal studies, scientists at Johns Hopkins have developed a fast and safe method for collecting heart stem cells from remarkably small amounts of biopsied heart tissue (15 mg or less), and growing the cells in the lab to get more.

The technique gets the job done within four weeks, producing enough stem cells to conceivably be used to repair heart tissue clinically. The resulting clusters, called cardiospheres, contain cells that retain the ability to regenerate themselves and to develop into more specialized heart cells that can conduct electrical currents and contract like heart muscle should.

Their findings, if affirmed in further clinical trials, could potentially offer patients a means of using their own stem cells to repair heart tissue soon after they have suffered a heart attack, or to regenerate weakened muscle resulting from heart failure, perhaps averting the need for heart transplants. By using a person's own adult stem cells instead of those from another donor, there would be no risk of triggering an immune response that could cause rejection.

Adult stem cells can be found in most living organ tissue, such as the heart, and can generally develop into related cell types, unlike embryonic stem cells that can become any type of cell or tissue in the body.

"Harnessing the potential benefits of therapy with adult stem cells is imperative if we are to make rapid progress in treating heart disease. Cardiac stem cells, grown from the heart itself, offer particular promise in that they can regenerate beating heart muscle," said Eduardo Marban, professor and chief of cardiology at the Johns Hopkins School of Medicine and its Heart Institute, and lead investigator of the study presented Nov. 8 at the American Heart Association's Scientific Sessions 2004. Marban is also director of the Johns Hopkins Institute of Molecular Cardiobiology.

"Our basic research is trying to overcome the biological problems in harnessing heart stem cells, so we are very excited about our success in growing and analyzing these cells," he said.

Using cardiac catheterization, where a tubelike probe is inserted into a vein in the neck that links to the heart, the Johns Hopkins team removed a small sample (15 mg or less) of heart tissue from the right ventricle in 23 patients already undergoing treatment for heart failure. Earlier studies in pigs found that adult stem cells were most abundant in this region of the heart. Most other researchers use invasive surgery to obtain larger portions of muscle tissue, to increase the number of adult stem cells harvested. An added benefit to catheterization is that it can be performed quickly, in less than 20 minutes.

The researchers then grew cells from the biopsy tissues to isolate heart stem cells and reproduce them in sufficient quantities, in excess of 100 million cells, that most think would be suitable for therapy.

"Our biopsy method was very effective, and within four weeks, most of the sample tissue produced enough heart stem cells for more advanced clinical testing," added Marban, who expanded this research at Johns Hopkins in June, based on initial studies from the University of Rome in 2002. The Rome team joined Johns Hopkins researchers in developing the latest study.

The scientists also studied pig heart stem cells and found that cardiospheres, when mixed with animal heart tissue in growth solutions, developed new cells that were able to conduct electricity and contract, two key properties of healthy heart tissue and a key feature to any potential long-term treatment of heart failure.

"Our next step is to test in animals whether these cells can survive and work properly in cases of heart attack and heart failure, using varying dose levels, while also monitoring the electrophysiology in a living heart," Marban said.

The study was funded by the Donald W. Reynolds Foundation. Other researchers who participated were Rachel Ruckdeschel Smith, M. Roselle Abraham, Elisa Messina, Alessandro Giacomello and Hee Cheol Cho.


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