In directing stem cells, study shows context matters

4 hours ago by Terry Devitt When blank slate stem cells are exposed to a soft as opposed to a hard surface on which to grow, they begin to transform themselves into neurons, the large, complex cells of the central nervous system. Absent any soluble factors to direct cell differentiation, surface matters, according to new research from the lab of University of Wisconsin-Madison chemist and biochemist Laura Kiessling. Credit: Kiessling Lab/UW-Madison

Figuring out how blank slate stem cells decide which kind of cell they want to be when they grow upa muscle cell, a bone cell, a neuronhas been no small task for science.

Human pluripotent stem cells, the undifferentiated cells that have the potential to become any of the 220 types of cells in the body, are influenced in the lab dish by the cocktail of chemical factors and proteins upon which they are grown and nurtured. Depending on the combination of factors used in a culture, the cells can be coaxed to become specific types of cells.

Now, in a new study published today, Sept. 8, in the Proceedings of the National Academy of Sciences, a team of researchers from the University of Wisconsin-Madison has added a new wrinkle to the cell differentiation equation, showing that the stiffness of the surfaces on which stem cells are grown can exert a profound influence on cell fate.

"To derive lineages, people use soluble growth factors to get the cells to differentiate," explains Laura Kiessling, a UW-Madison professor of chemistry and biochemistry and stem cell expert.

Past work, she notes, hinted that the qualities of the surface on which a cell lands could exert an influence on cell fate, but the idea was never fully explored in the context of human pluripotent stem cell differentiation.

In the lab, stem cells are grown in plastic dishes coated with a gel that contains as many as 1,800 different proteins. Different factors can be introduced to obtain certain types of cells. But even in the absence of introduced chemical or protein cues, the cells are always working to differentiatebut in seemingly random, undirected ways.

The Wisconsin group, directed by Kiessling and led by chemistry graduate student Samira Musah, decided to test the idea that the hardness of a surface can make a difference. After all, in a living body, cells seek different niches with different qualities and transform themselves accordingly.

"Many cell types grow on a surface. If a cell is near bone, the environment has certain features," says Kiessling, whose groupcollaborating with UW-Madison colleagues Sean Palecek, Qiang Chang and William Murphyhas been working to produce precise, chemically defined surfaces on which to grow stem cells. "A cell will react differently if it lands near soft tissue like the brain."

To fully explore the idea that surface matters to a stem cell, Kiessling's group created gels of different hardness to mimic muscle, liver and brain tissues. The study sought to test whether the surface alone, absent any added soluble factors to influence cell fate decisions, can have an effect on differentiation.

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In directing stem cells, study shows context matters