Scientists want to unravel the complex combination of chemical and physical cues that choreograph stem cell behavior. Now researchers have used a simple nanoscale technique to add texture to glass slides and have shown that human embryonic stem cells grown on smooth surfaces behave differently than those grown on rough ones (ACS Nano, DOI: 10.1021/nn3004923). Understanding the conditions that affect stem cell growth and differentiation could lead to regenerative medicine applications such as replacing damaged tissues with lab-grown ones, experts say.
Doctors and scientists believe that human embryonic stem cells present tremendous promise as tools for biomedical research and as future therapies for chronic diseases and spinal cord injuries. Previously, researchers had discovered how the shape and texture of the environment influence the behavior of adult stem cells, which are partially differentiated cells that can become a limited set of cells within the body. Embryonic stem cells retain the flexibility to produce any type of human cell, but they are notoriously finicky to culture. To produce large, high quality batches of these cells for research or tissue engineering, researchers need to understand the mechanical signals that influence their division and differentiation, says Jianping Fu of the University of Michigan, Ann Arbor.
To examine how the texture of a surface affects these cells, Fu and his colleagues used an inexpensive technique called reactive ion etching to score patterns of tiny rough spots on a glass slide’s surface. The researchers could control the layout of the rough spots by changing the pattern in a template they laid on the slide. They then watched human embryonic stem cells grow on the slides for 48 hours. Embryonic stem cells on smooth slides flourished: They divided rapidly and retained their ability to become any cell type. Stem cells seeded on rougher surfaces divided more slowly, and in some cases, began the process of differentiation into specific cell types.
The researchers then compared the behavior of stem cells on these surfaces with that of fibroblasts, which are differentiated cells in connective tissue. Fibroblasts grew better in the rough areas, which suggests that such surfaces could separate cell types based on their level of differentiation, Fu says.
The researchers wanted to know how the surface roughness triggers changes inside the cells, so they looked to the cell membrane. On their membranes, cells form focal adhesions, which are groupings of proteins that cells use to attach themselves to their surroundings and to receive and send biochemical information. In the cell culture experiments, when embryonic stem cells grew on smooth surfaces, the structures formed at the edges where cells met other cells. On rough surfaces, cells’ focal adhesions dotted their membranes. Fu and his colleagues don’t yet understand what causes these different patterns – or how the patterns affect cell behavior. But they saw differences, depending on surface texture, in the cells’ expression of E-cadherin, a protein that regulates contacts between stem cells. The researchers suggest that the protein could link the physical cues with the cell’s biochemistry.
The research “offers valuable insight” about how surface roughness influences behavior and about how a cell might sense that roughness, says Eben Alsberg of Case Western Reserve University. This understanding could help researchers develop tissues for regenerative medicine from the cells, he adds.