Differentiation is the process of stem cells morphing into other types of cells. Understanding it is key to developing future stem cell-based regenerative therapies.
"We show, for the first time, that we can predict stem cell differentiation as early as Day 1," said Jianping Fu, an assistant professor in mechanical engineering and biomedical engineering who is the first author on the paper."Normally, it takes weeks or maybe longer to know how the stem cell will differentiate. Our work could speed up this lengthy process and could have important applications in drug screening and regenerative medicine. Our method could provide early indications of how the stem cells are differentiating and what the cell types they are becoming under a new drug treatment."
"Our research confirms that mechanical factors are as important as the chemical factors regulating differentiation," Fu said. "The mechanical aspects have, until now, been largely ignored by stem cell biologists."
The researchers built a novel type of stem cell matrix, or scaffold, whose stiffness can be adjusted without altering its chemical composition, which cannot be done with conventional stem cell growth matrices, Fu said.
The new scaffold resembles an ultrafine carpet of "microposts," hair-like projections made of the elastic polymer polydimethylsiloxane---a key component in Silly Putty, Fu said. By adjusting the height of the microposts, the researchers were able to adjust the rigidity of the matrix.
Using a technique called fluorescent microscopy, the researchers measured the bending of the microposts in order to quantify the traction forces.
"Our study shows that if the stem cells determine to differentiate into one cell type then their traction forces can be much greater than the ones that do not differentiate, or that differentiate into another cell type," Fu said. "We prove that we can use the evolution of the traction force as early indicators for stem cell differentiation."
The new matrix---manufactured through an inexpensive molding process---is so cheap to make that the researchers are giving it away to any interested scientists or engineers.
"We think this toolset provides a newly accessible, practical methodology for the whole community," Fu said.
The paper is called "Mechanical regulation of cell function using geometrically modulated elastomeric substrates." This work was conducted in Dr. Christopher Chen's group in the Department of Bioengineering at the University of Pennsylvania. The research was supported by the National Institutes of Health and the American Heart Association.
For more information on Jianping Fu's Integrated Biosystems and Biomechanics Lab, visit http://me.engin.umich.edu/ibbl.
The University of Michigan College of Engineering is ranked among the top engineering schools in the country. At $160 million annually, its engineering research budget is one of largest of any public university. Michigan Engineering is home to 11 academic departments and a National Science Foundation Engineering Research Center. The college plays a leading role in the Michigan Memorial Phoenix Energy Institute and hosts the world-class Lurie Nanofabrication Facility. Michigan Engineering's premier scholarship, international scale and multidisciplinary scope combine to create the Michigan Difference. Find out more at www.engin.umich.edu.
EDITORS: Photos are available at http://www.ns.umich.edu/Releases/2010/Jul10/micropost.html
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