Many stem-cell researchers hope to treat diseases by recruiting these adaptable cells to replace others that have been damaged. A report published today in Science demonstrates a different approach, which rescued mice that otherwise would have died from a genetic heart defect before birth. Instead of replacing the defective cells, embryonic stem (ES) cells released chemical signals that caused the defective heart tissue to grow properly.
Complex structures like the heart or blood vessels arise from intricate chemical choreography that tells growing cells what to become and when. Tumors hijack this system to build blood vessels for themselves. Senior author Robert Benezra of the Memorial Sloan-Kettering Cancer Center has been studying a group of proteins called Id, which help control development by turning genes on and off. To find out more about how these proteins affect blood vessel growth, Benezra's team used ¿knock-out¿ mice, in which genes for Id proteins were deactivated.
Mouse embryos that lack multiple Id proteins die before birth because the wall of the heart is too thin. To buy themselves more time to study the blood vessels, the researchers injected 15 normal ES cells into early mouse embryos. About half of the embryos actually survived past birth, and exhibited normal-looking hearts. ¿It came as a complete shock to us that they were born. We were just hoping to extend their lives by a day or two,¿ Benezra says.
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Descendants of the injected ES cells accounted for just one in five cells in the rescued hearts, so the injected cells had not simply taken over. Instead, the researchers determined, exposure to two chemicals secreted by the ES cells prompted the defective cells to start producing different set of proteins and develop properly. One of these chemicals even reached the embryo across the placenta from ES cells injected earlier into the mother.
Exploiting the signaling molecules secreted by ES cells, rather than the cells themselves, may someday form the basis for new treatment. For example, molecules might be used directly, or the ES cells might be employed to deliver these healing chemicals to where they are needed. Still, ¿the first challenge is to see how general this is,¿ Benezra cautions. In a commentary accompanying the Science report, Kenneth Chien, Alessandra Moretti and Karl-Ludwig Laugwitz suggest that other stem-cell researchers should make certain to check whether their results arise from the cells themselves, or from chemicals the cells may be secreting. This new finding, Chien remarks, is ¿one of the most exciting discoveries in the field of cardiac stem cells to date.¿