University of Pennsylvania Researchers: Adult Stem Cells Are Touchy-Feely, Need Environmental Clues for Change

PHILADELPHIA  -- A certain type of adult stem cell can turn into bone, muscle, neurons or other types of tissue depending on the feel of their physical environment, according to researchers at the University of Pennsylvania. The researchers discovered that mesenchymal stem cells, which regularly reside in the bone marrow as part of the bodys natural regenerative mechanism, depend on physical clues from their local environment in order to transform into different types of tissue.  The researchers were even able to manipulate stem cells by changing the firmness of the gel on which they were grown.

The findings, which appear in the Aug. 25 issue of the journal Cell, have implications for the use of adult stem cells in medical treatments.  It may even be possible to prepare stem cells for transplant in the laboratory by growing them in the right physical setting beforehand.

"Basically, mesenchymal stem cells feel where they're at and become what they feel, said Dennis Discher, a professor in Penn's School of Engineering and Applied Science and a member of Penns Institute or Medicine and Engineering.  The results begin to establish a physical basis for both stem cell use against diseases and for stem cell behavior in embryonic development.

Much of the work in stem cell science has involved the study of the chemical microenvironment  the soup of chemical messenger signals that are generally thought to guide stem cells through the process of differentiation, where relatively blank stem cells turn into specific cell types.  For the first time, the Penn researchers have proven that the physical microenvironment is also crucial for guiding the cells through differentiation.

According to the researchers, soft microenvironments that mimic the brain guide the cells toward becoming neurons, stiffer microenvironments that mimic muscle guide the cells toward becoming muscle cells and comparatively rigid microenvironments guide the cells toward becoming bone.

Mesenchymal stem cells sense their environment through the force it takes them to push against surrounding objects.  Each cell has its own skeleton and molecular motors that it uses as muscles.  According to Discher and his colleagues, the amount of force the stem cell needs to move its cellular muscles triggers an internal chemical signal that, in turn, causes the cell to differentiate.

The cytoskeleton uses motors that, like our muscles, are based on the mechanical tension created by molecules of actin and myosin, Discher said. When we deprive these stem cells of myosin, the cells do not respond to its physical environment, only the its chemical environment.  

Unfortunately, the physical microenvironment can change due to injury, which would make it difficult to use these stem cells in certain types of therapy.  After a heart attack, for example, the heart becomes so scarred that stem cells seem ineffective in fixing the damage by turning into replacement cardiac muscle.

The cardiac cells may have been damaged so much during the heart attack that the stem cells do not recognize the microenvironment as a guide for turning into heart muscle, Discher said. However, our studies show that it might be possible to prime stem cells for therapy in the lab, before implanting them in the heart, spine, or whatever damaged environment you want to place them.

Penn researchers included in this study include Adam J. Engler and Shamik Sen from the School of Engineering and Applied Science and H. Lee Sweeney from the School of Medicine.

Funding for this research was provided by the National Institutes of Health, Muscular Dystrophy Association, National Science Foundation and the Ashton Foundation.