One Stem Cell Fact You Need to Know

Everyone who works with stem cells knows that human pluripotent stem cells can become any of the 220 cells in the body. Undifferentiated cells are influenced by the chemicals in the lab dish in which they are grown. By using different chemicals, researchers can direct the cells to become whatever kind of cells they want.

Terry Devitt, writing for University of Wisconsin News, reports that something other than the chemicals in the petri dish affects cell differentiation. The hardness of the surfaces on which stem cells are grown also exerts a profound influence on the cells’ fate.

“Investigators use soluble growth factors to get the cells to differentiate, ” explained Laura Kiessling, Ph.D., a UW-Madison professor of chemistry and biochemistry and stem cell expert. She and her associates grow stem cells in plastic dishes coasted with a gel that may contain as many as 1, 800 different proteins. She says that, whether or not the gel contains proteins, the cells are always working at becoming something—but in seemingly random ways.

Kiessling, noting that cells appeared to react to the surfaces near to them, decided to find out if the quality of a surface mattered to a stem cell. According to DeVitt, her group created gels of different hardness to mimic muscle, liver and brain tissues. They also wanted to find out if the surface alone, without any added proteins or chemicals, would influence cell fate decisions and have an effect on differentiation.

The results, Kiessling reported, showed that a soft, brain tissue-like surface, independent of any soluble factors, was catalyst enough to direct cells to become neurons, the large elaborate cells that make up the central nervous system. “We didn’t change anything but switch from a hard surface to a soft surface, ” Kiessling says. “They all started looking like neurons. It was stunning to me that the surface had such a profound effect.”

Devitt reported that the Wisconsin researchers believe that the mechanical properties of a surface are influencing a protein called YAP. YAP is found in the cytoplasm and the nucleus of a cell, and when it is in the nucleus, YAP regulates gene expression. According to the study results, YAP is excluded from the nucleus on the soft gels, and its depletion there helps drive the stem cells onto a brain cell developmental pathway.

Kiessling’s group’s finding, that the simple mechanical properties of a surface can play a major role in helping stem cells decide what to be, may—in her opinion—inform the methods used for producing large quantities of cells for therapeutic use.