May 18, 2004 NEW YORK -- Embryonic stem cells may hold the key to regenerating damaged heart muscle, when transplanted within a 3-dimensional scaffold into the infracted heart, according to a new study coming out in June in the Journal of Heart and Lung Transplantation. In the study, embryonic stem cells were more successful in restoring heart muscle when transplanted within a 3-dimensional matrix into damaged hearts in an animal model of severe infarction.
The new study addresses several problems that have plagued previous attempts to regenerate damaged heart muscle, according to Theo Kofidis, M.D., who has an active tissue engineering program at Stanford.
"Tissue engineering holds out promise of truly healing the heart after congestive heart failure," said Dr. Kofidis, lead author of the study and research fellow in cardiothoracic surgery at the Falk Research Center at Stanford University Medical School in Stanford, Calif. "There are 460,000 cases of congestive heart failure in the United States each year and the preeminently efficient treatment we have at this time is heart transplantation. Through tissue engineering we could actually restore the function of the heart by replacing large portions of the damaged heart muscle by a bioartificial one."
Dr. Kofidis spoke today at an American Medical Association media briefing on cardiology in New York City.
Kofidis and his colleagues had been working with bone marrow stem cells, but these cells were not able to become heart muscle cells and regenerate the heart. "In our most recent studies we showed that mouse and human embryonic stem cells improved heart function, had superior survival within the heart – weeks later we still saw improved heart function – and had definitely differentiated into heart muscle cells," he said. "We inserted a bioluminescent marker (what causes fireflies to luminesce) into our stem cells and were able to see that they engrafted in the living organ."
There are two components to tissue engineering, according to Dr. Kofidis: the cells that will replace the dead cells and regenerate the organ, and the supporting framework that will distribute the cells evenly and maintain the 3-D shape necessary for proper functioning of the organ.
"We have been working for a long time on developing the ideal scaffolding to support the injected cells and the architecture of the organ," said Dr. Kofidis. "We have identified a collagen, a mesh-like structure, that we have manipulated into an excellent framework. The cells distribute evenly into this meshwork, which is a liquid. Then, due to its liquid nature, we are able to inject it into the heart through an endoscope, with much less surgical trauma than if we had to open the chest to reach the heart. This liquid tissue solidifies at body temperature.
"We let Nature integrate this tissue," said Dr. Kofidis. "We inject it as a liquid and let it consolidate within the affected heart where it supports the geometry of the damaged region. One of the problems in congestive heart failure is that the wall of the heart's chamber becomes thinner and thinner as the heart muscle cells die off. Eventually it is too weak to beat properly."
With the integration of the human embryonic stem cells and their patented supporting framework, Kofidis hopes that they have the two pieces of the puzzle needed to successfully integrate regenerative cells into the damaged heart, maintain its geometry and restore its function.
"A word of warning may be appropriate here. Only a few years ago many people thought an artificial heart was around the corner," said Dr. Kofidis. "We now know that there are many problems to overcome and questions to answer. In order to reproduce nature with the highest possible fidelity we have to build something that follows the natural architecture of the heart."
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