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APRIL 2005

Human Stem Cells Can Develop Into Functional
Muscle Tissue

The discovery by Weill Medical College of Cornell University researchers that a specific type of human fetal stem cell can co-differentiate simultaneously into both muscle and blood vessel cells may unlock the door to therapies that replace damaged tissue in the heart and other organs. This finding could be a breakthrough in using stem cells to repair damaged hearts.

Heart attacks and other events can destroy cardiac muscle and the surrounding vasculature (blood vessels). Effective heart repair requires concurrent replacement of both these types of tissues. The new finding moves us one big step closer to that goal, the investigators say.

“This discovery comes at a time when research into these types of stem-cell-based regenerative therapies have faced major hurdles,” said Dr. Shahin Rafii, Arthur B. Belfer Professor of Genetic Medicine and newly announced Howard Hughes Medical Institute (HHMI) investigator at Weill Cornell Medical College in New York City.

Dozens of papers have confirmed the potential of bone-marrow-derived stem cells to develop into cardiac tissue cells, and for a while it looked like purified stem cells from adult bone marrow might do the trick. However, those hopes were dashed last spring, when a group of researchers found the ability of these stem cells to incorporate into ailing heart tissue was much less robust than originally thought.

“So, it was Ôback to the drawing board’ for this type of stem-cell research,” said study lead author Dr. Sergey V. Shmelkov, postdoctoral fellow working in Dr. Rafii’s lab. Fortunately, for almost five years, the Weill Cornell team had evidence that a specific type of stem cell—bearing a surface antigen called CD133—was unusually adept at differentiating (developing) into a myriad of organ-specific cell types. While cells bearing this CD133 biomarker are very rare in adult tissues, they are particularly abundant in the fetal liver.

“We wondered if, given the right conditions, these cells might fulfill the requirement of growing into both myocytes (muscle cells) and angiogenic (blood-vessel-wall) cells, both of which are needed for efficient heart repair,” Dr. Shmelkov explained.

Using human fetal liver tissues, the Weill Cornell team isolated CD133+ stem cells, and then bathed them in a culture rich in growth factors and other biochemicals. “Importantly, only stem cells with the CD133 antigen developed into endothelial blood vessel cells and myocytes,” Dr. Rafii said. “Stem cells without this surface antigen failed to do so.”

“This is really an important discovery,” Dr. Shmelkov said, “Because it proves that, given the right micro-environmental clues, we can encourage the regrowth of vascularized heart tissue. Muscle cells need vasculature to grow and survive, so we need to find stem cells capable of forming both myocytes and angiogenic cells. We think we’ve found them.”

“All of these findings are re-igniting interest in using these biochemically activated stem cells to regenerate vascularized tissue,” Dr. Rafii said. “Some of our research may even help find new sources of expandable CD133+ stem cells within umbilical cord blood or adult bone marrow, livers, or other organs.”

“Each year thousands of adults succumb to heart attack. We hope our study will provide the impetus to initiate clinical trials that can help ease the tremendous physical and socio-economic burden caused by vascular diseases,” he added. #

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