Human embryonic stem cells prefer to grow on a soft, ultrafine carpet, made of a key ingredient in Silly Putty, according to a University of Michigan study published online in Nature Materials. Researchers found that the sponginess of the environment where the cells were growing affected the type of specialized cells they eventually became. Cells grown on a soft bed turned into working spinal cord cells faster and more efficiently than those grown on a firmer surface.
The study, led by Jianping Fu, Ph.D., an assistant professor of mechanical engineering, is the first to directly link physical, as opposed to chemical, signals to human embryonic stem cell differentiation .In the specially engineered growth system that Fu and his colleagues designed, microscopic posts of the Silly Putty component polydimethylsiloxane serve as the threads on a kind of carpet. By varying the posts’ height, the researchers could adjust the stiffness of the surface they grew the cells on. Shorter posts were more rigid—as on an industrial carpet. Taller ones were softer.
The team found that stem cells grown on the tall, softer micropost carpets turned into nerve cells much faster and more often than those they grew on the stiffer surfaces. After 23 days, the colonies of spinal cord cells—motor neurons that control how muscles move—that grew on the softer micropost carpets were four times more pure and 10 times larger than those growing on either traditional plates or rigid carpets.
“This is extremely exciting, ” Fu says. “To realize promising clinical applications of human embryonic stem cells, we need a better culture system that can reliably produce more target cells that function well. Our approach is a big step in that direction, by using synthetic microengineered surfaces to control mechanical environmental signals.”
Fu’s findings may go deeper than cell counts. The researchers verified that the new motor neurons they obtained on soft micropost carpets showed electrical behaviors comparable to those of neurons in the human body. They also identified a signaling pathway involved in regulating the mechanically sensitive behaviors. Fu believes that their findings raise the possibility of a more efficient way to guide stem cells to differentiate and potentially provide therapies for diseases such as amyotrophic lateral sclerosis (ALS).
Eva Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the University of Michigan, studies amyotrophic lateral sclerosis. She believes stem cell therapies—both from embryonic and adult varieties—might help patients grow new nerve cells. She is presently using Fu’s technique to try to make fresh neurons from patients’ own cells.
“Prof. Fu and colleagues have developed an innovative method of generating high-yield and high-purity motor neurons from stem cells, ” Feldman says. “For ALS, discoveries like this provide tools for modeling disease in the laboratory and for developing cell-replacement therapies, ” she said.
