Mouse embryonic stem cells can work to build the heart, potentially moving medical science a step closer to a new generation of heart-disease treatments that use human stem cells, School of Medicine research shows.
The scientists reported in a recent issue of Cell Stem Cell that the Mesp1 gene locks mouse embryonic stem cells into becoming heart parts and moves them to the area where the heart forms. Researchers are now testing if stem cells exposed to Mesp1 can help fix damaged mouse hearts.
“This isn’t the only gene we’ll need to get stem cells to repair damaged hearts, but it’s a key piece of the puzzle,” said senior author Kenneth Murphy, M.D., Ph.D., professor of pathology and immunology and a Howard Hughes Medical Institute investigator.
“This gene is like the first domino in a chain: The Mesp1 protein activates genes that make other important proteins, and these in turn activate other genes and so on. The end result of these falling genetic dominoes is your whole cardiovascular system.”
Embryonic stem cells have created considerable excitement because of their potential to become almost any specialized cell type. Scientists hope to use stem cells to create new tissue to treat diseases and injuries. But first they have to learn how to coax them into becoming specialized types such as nerve cells, skin cells or heart cells.
“That’s the challenge to realizing the potential of stem cells,” Murphy said. “We know some things about how the early embryo develops, but we need to learn a great deal more about how factors like Mesp1 control the roles that stem cells assume.”
Using mouse embryonic stem cells, Murphy’s lab showed that Mesp1 starts the development of the cardiovascular system and that the gene’s protein helps generate an embryonic cell layer known as the mesoderm, from which the heart, blood and other tissues develop. Mesp1 also triggers the creation of atype of cell recently recognized as the heart’s precursor.
They also found that stem cells exposed to the Mesp1 protein are locked into becoming one of three cardiovascular cell types: endothelial cells, which line the interior of blood vessels; smooth muscle cells, which are part of the walls of arteries and veins; or cardiac cells, which make up the heart.
“After they are exposed to Mesp1, the stem cells don’t make any decisions for several days as to which of the three cell types they’re going to become,” Murphy said. “The cues that cause them to make those commitments come later from proteins from other genes.”