he physical environment might limit the fate of stem cells, I never really thought that it would be sufficient to direct cell fate," said Lee Sweeney, a coauthor of the study and chairman of Physiology in Penn's School of Medicine. "When I saw Adam's first images, I was stunned to see that the physical environment alone was telling the stem cells to become neurons or muscle or bone. "
Mesenchymal stem cells sense their environment through the force it takes them to push against surrounding objects. Each cell has its own skeleton and molecular motors that it uses as muscles. According to the researchers, the amount of force the stem cell needs to move its cellular muscles triggers an internal chemical signal that, in turn, directs the cell to differentiate.
"The cytoskeleton uses motors that, like our muscles, are based on the mechanical tension created by molecules of actin and myosin," Engler said. "When we deprive these stem cells of myosin, the cells do not respond to their physical environment, only their chemical environment."
But, the physical microenvironment can change due to injury and also in disease, which would make it difficult to use these stem cells in certain types of therapy. After a heart attack, for example, the heart becomes so scarred that stem cells seem ineffective in fixing the damage by turning into replacement cardiac muscle.
"The cardiac tissue may have been so damaged during the heart attack that the stem cells do not recognize the microenvironment as a guide for turning into heart muscle," Discher said; "however, our studies show that it might be possible to 'prime' stem cells for therapy in the lab, before implanting them in the heart, spine or whatever damaged environment you want to place them."
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