Helping Cultured Stem Cells Roll
Researchers who study mesenchymal stem cells know that these cells hold enormous therapeutic potential to differentiate on cue into new bone or cartilage-forming cells that can regenerate damaged tissue. It is tricky to deliver these cells reliably to a site of injury or inflammation, preferably via direct infusion into the bloodstream. The problem is that typically less than 1% of cultured mesenchymal stem cells have the ability to home in on their target once infused into the blood system. The reason: In culture, most either lose or do not possess the needed homing receptors that typically must be displayed on the cell surface of mesenchymal stem cells. This shortcoming has led to various strategies to coax more cultured mesenchymal stem cells not only to find their targets, but also to adhere to them. However, the mesenchymal stem cells in the blood stream arrive via a rolling landing onto their target tissue. This landing helps the stem cells to decelerate and initiate the subsequent steps in the adhesion cascade, including firm adhesion and passage into the tissue. Current strategies have yet to mimic this natural rolling landing and trigger the natural adhesion cascade. A team of National Institute of Dental and Craniofacial Research (NIDCR) grantees and colleagues previously developed a versatile cell-engineering approach that allowed them to attach adhesion molecules to the surface of stem cells, improving their rolling response and thus homing ability. Now they are taking the next step in engineering mesenchymal stem cells with self-assembled lipid vesicles on their surface that transiently present molecules that promote cell rolling. “This method presents an alternative cell membrane engineering approach to introduce a ligand of interest on the cell membrane for short duration, in contrast to enzymatic and covalent modification methods….offers a platform that can be used to investigate engineered stem cell homing and interrogate the biology of cell homing.”
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