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Embryonic stem cells correct congenital heart defect in mouse embryos

NEW YORK, NY - A study published in the October 8 issue of Science describes a previously unsuspected capacity of embryonic stem cells to influence neighboring defective cells and restore their capacity to function normally.

Researchers at Memorial Sloan-Kettering Cancer Center report that 15 embryonic stem cells injected into early embryos of mice whose hearts were genetically predisposed to develop a lethal defect, rescued the heart from developing the disorder by not only producing normal daughter cells that were incorporated into the defective embryonic heart but also by releasing biological factors into the nearby vicinity. This prevented neighboring heart cells from developing into defective tissue.

"In other words, stem cells act like nurses, restoring 'sick' cells to health" said Robert Benezra, Ph.D., a Member in the Cancer Biology and Genetics Program at Memorial Sloan-Kettering Cancer Center and the study's senior author. "The result was that fifty-percent of the mice fated to die in the womb were born with healthy hearts."

In previous studies, Dr. Benezra and colleagues demonstrated a relationship between the presence of a specific protein called Id during embryonic growth and the normal development of capillaries and blood vessels. Mice engineered without this protein, called Id "knock-out" mice, display severe cardiac defects and die at mid-gestation.

"In this current study, with the repair of congenital heart defects in our Id knockout embryos, we observed that the stem cells provided normal signals to themselves and also to their neighbor cells to correct the organ as a whole," explained Diego Fraidenraich, Ph.D., the study's lead author.

The researchers also found a relationship between the Id protein and stem cells. "We found that stem cells are critically dependent on the Id protein for self-renewal and differentiation," added Dr. Benezra. "A reduction of just 15-20 percent of the Id protein impairs the s
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Contact: Joanne Nicholas
nicholaj@mskcc.org
212-639-3573
Memorial Sloan-Kettering Cancer Center
7-Oct-2004


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