At the Meeting: Putting the Squeeze on Stem Cells

Newswise — "Location, location, location," the great axiom of real estate value, may also apply to the fate of stem cells. Simply by assigning human mesenchymal stem cells ample or limited growing room, researchers at Johns Hopkins University School of Medicine led by Christopher S. Chen can control what these progenitor cells will be when they grow up. Given space to spread out, mesenchymal stem cells develop into osteoblasts (bone cells). Given narrow quarters, they become adipocytes (fat cells). Chen's paper, to be delivered at the American Society for Cell Biology's 43rd Annual Meeting in San Francisco, is the first demonstration that a simple mechanical cue, available space, can influence mesenchymal stem cell differentiation. Human mesenchymal stem cells can be isolated from adult bone marrow. These stem cells have the potential to become ('differentiate into') different kinds of cells found in connective tissues including bone, fat, skeletal muscle, tendon and cartilage cells. Researchers typically cause stem cells to differentiate by exposing them to specific growth factors. However given the mechanical functions of these tissues, particularly bone and cartilage, Hopkins' Christopher S. Chen hypothesized that mesenchymal stem cells might respond to physical pressure in their surroundings. To tackle this question, graduate student Rowena McBeath adapted a technique from the microchip industry called "micropatterning." She used plastic chips printed with tiny "islands" so small that a single stem cell can be cultured on each island. McBeath could precisely determine how much room each cell had to spread out, by assigning it to a large or small island. Stem cells placed on large islands spread out to the edges, adhered tightly and 'pulled' (contracted) against the island perimeter. In contrast, cells on small islands stayed round and relaxed in the center of the island.

Why did extra space cause stem cells to become bone cells? In a second experiment, McBeath activated stem cell contractility not by microchip islands, but by activating RhoA, a protein that increases tension in the cytoplasm. Stem cells with activated RhoA tightened up and became bone cells. These findings may lead to better ways to improve the healing of bone fractures, say the researchers. These findings have further implications for astronauts, who are prone to multiple bone fractures after returning from long space journeys, and may explain why mild weight-lifting exercises can lower fracture rates in senior citizens. Location, location, and gravity may be the pressure needed to push mesenchymal stem cells to choose a bony fate over a fat one.

RhoA, Cell Shape, and Cytoskeletal Tension Cooperate to Regulate Stem Cell Lineage Commitment, R. McBeath,1 D. Pirone,2 C. Nelson,2 C. S. Chen2; 1 Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 2 Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD.