Stem cell fate depends on ‘grip’
Mar. 28, 2013 The field of regenerative medicine holds great promise, propelled by greater understanding of how stem cells differentiate themselves into many of the body's different cell types. But clinical applications in the field have been slow to materialize, partially owing to difficulties in replicating the conditions these cells naturally experience.
A team of researchers from the University of Pennsylvania has generated new insight on how a stem cell's environment influences what type of cell a stem cell will become. They have shown that whether human mesenchymal stem cells turn into fat or bone cells depends partially on how well they can "grip" the material they are growing in.
The research was conducted by graduate student Sudhir Khetan and associate professor Jason Burdick, along with professor Christopher Chen, all of the School of Engineering and Applied Science's Department of Bioengineering. Others involved in the study include Murat Guvendiren, Wesley Legant and Daniel Cohen.
Their study was published in the journal Nature Materials.
Much research has been done on how stem cells grow on two-dimensional substrates, but comparatively little work has been done in three dimensions. Three-dimensional environments, or matrices, for stems cells have mostly been treated as simple scaffolding, rather than as a signal that influences the cells' development.
Burdick and his colleagues were interested in how these three-dimensional matrices impact mechanotransduction, which is how the cell takes information about its physical environment and translates that to chemical signaling.
"We're trying to understand how material signals can dictate stem cell response," Burdick said. "Rather than considering the material as an inert structure, it's really guiding stem cell fate and differentiation -- what kind of cells they will turn into."
The mesenchymal stem cells the researchers studied are found in bone marrow and can develop into several cell types: osteoblasts, which are found in bone; chondrocytes, which are found in cartilage; and adipocytes, which are found in fat.
The researchers cultured them in water-swollen polymer networks known as hydrogels, which share some similarities with the environments stem cells naturally grow in. These materials are generally soft and flexible -- contact lenses, for example, are a type of hydrogel -- but can vary in density and stiffness depending on the type and quantity of the bonds between the polymers. In this case, the researchers used covalently cross-linked gels, which contain irreversible chemical bonds.
When seeded on top of two-dimensional covalently cross-linked gels, mesenchymal stem cells spread and pulled on the material differently depending on how stiff it was. Critically, the mechanics guide cell fate, or the type of cells they differentiate it into. A softer environment would produce more fat-like cells and a stiffer environment, where the cells can pull on the gel harder, would produce more bone-like cells.
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Stem cell fate depends on 'grip'