Adult Stem Cells Are Touchy-feely, Need Environmental Clues

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Adult Stem Cells Are Touchy-feely, Need Environmental Clues

http://www.medicalnewstoday.com/medicalnews.php?newsid=50450

A certain type of adult stem cell can turn into bone, muscle, neurons

or other types of tissue depending on the " feel " of its 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 body's 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 researchers believe that their findings, which appear in the Aug.

25 issue of the journal Cell, could change the way in which people

work with stem cells.

" 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. " 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 Adam Engler, the

first author on the study and a graduate student in the School of

Engineering and Applied Science, 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.

" While I anticipated that the physical environment might limit the

fate of stem cells, I never really thought that it would be

sufficient to direct cell fate, " said Lee Sweeney, a coauthor of the

study and chairman of Physiology in Penn's School of Medicine. " When

I saw Adam's first images, I was stunned to see that the physical

environment alone was telling the stem cells to become neurons or

muscle or 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

the researchers, the amount of force the stem cell needs to move its

cellular muscles triggers an internal chemical signal that, in turn,

directs 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, "

Engler said. " When we deprive these stem cells of myosin, the cells

do not respond to their physical environment, only their chemical

environment. "

But, the physical microenvironment can change due to injury and also

in disease, 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 tissue may have been so damaged 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. "

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Penn researchers involved in this study also include Shamik Sen from

the School of Engineering and Applied Science. Funding for this

research was provided by the National Institutes of Health, the

Muscular Dystrophy Association and the National Science Foundation