Silly Putty Component Used to Help in Stem Cell Therapies

The sponginess of the setting where human embryonic stem cells are growing, affects the type of specialized cells they will ultimately become, new research shows. Scientists persuaded human embryonic stem cells to convert into working spinal cord cells more effectively by growing the cells on a soft, ultrafine carpet made of a key ingredient in Silly Putty [a substance with unusual properties based on silicone polymers, used as a toy].

The study’s findings were published online April 13, 2014, in the journal Nature Materials. This research is the first to directly link physical, instead of chemical, signals to human embryonic stem cell differentiation. Differentiation is the process of the source cells morphing into the body’s more than 200 cell types that become bone, muscle, nerves, and organs.

Jianping Fu, a University of Michigan (U-M; Ann Arbor, USA) assistant professor of mechanical engineering, noted that the findings offer the potential of a more effective way to guide stem cells to differentiate and potentially provide therapies for diseases such as amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease), Huntington’s, or Alzheimer’s.

In the specially modified growth system, the “carpets,” Prof. Fu and his colleagues designed microscopic posts of the Silly Putty component polydimethylsiloxane to serve as the threads. By varying the post height, the researchers can adjust the stiffness of the surface they grow cells on. Shorter posts are more rigid—similar to an industrial carpet. Taller ones are softer—more plush.

The scientists found that stem cells they grew on the tall, softer micropost carpets turned into nerve cells much faster and more frequently than those they grew on the stiffer surfaces. After 23 days, the colonies of spinal cord cells—motor neurons that regulate 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,” Prof. Fu said. “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.”

Prof. Fu is collaborating with physicians at the U-M Medical School. Eva Feldman, a professor of neurology, studies amyotrophic lateral sclerosis (ALS), which paralyzes patients as it kills motor neurons in the brain and spinal cord.

Researchers such as Prof. Feldman believe stem cell therapies—both from embryonic and adult varieties—might help patients grow new nerve cells. The researchers technique to try to generate fresh neurons from patients’ own cells. At this point, they are examining how and whether the process could work, and they hope to try it in humans in the future. “Prof. Fu and colleagues have developed an innovative method of generating high-yield and high-purity motor neurons from stem cells,” Prof. Feldman said. “For ALS, discoveries like this provide tools for modeling disease in the laboratory and for developing cell-replacement therapies.”

Prof. Fu’s findings 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. A signaling pathway is a route through which proteins ferry chemical messages from the cell’s borders to deep inside it. The pathway they narrowed in on, called Hippo/YAP, is also involved in controlling organ size and both causing and preventing tumor growth.

Prof. Fu reported that his findings could also provide clues into how embryonic stem cells differentiate in the body. “Our work suggests that physical signals in the cell environment are important in neural patterning, a process where nerve cells become specialized for their specific functions based on their physical location in the body,” he said.

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