Their experiments revealed that, similar to white blood cells that act during an immune response, MSCs use inflammation-specific adhesion molecules called vascular cell adhesion molecule-1 (VCAM-1) to stick to the endothelium at sites of inflammation. "But," says Carman, "whereas white cells very efficiently crawl over the endothelial surface, apparently searching out weak spots to breach and migrate across this barrier, we discovered that MSCs are unable to mediate such crawling and are about 10 times slower to cross the endothelium." And that, he adds, may explain why MSCs are not efficient at entering inflamed tissues.
"This work suggests that the initial phase of the homing cascadecell rollingis the rate limiting step to achieve effective homing for MSCs," says Karp, Co-Director of the Center for Regenerative Therapeutics at BWH, and Associate Professor of Medicine at HMS. (Homing occurs when circulating MSCs target areas of injury in response to signals of cellular damage; cell rolling refers to the way that MSCs "decelerate" on this target tissue.)
"Clinically this would be a good place to focus efforts to enhance MSC homingto improve the ability to roll on inflamed endothelium, since we showed that MSCs can efficiently adhere under static conditions and transmigrate on the endothelium in inflamed tissues," adds Karp, who is also a principal faculty member of the Harvard Stem Cell Institute.
The scientists further discovered that when MSCs do eventually cross the endothelium, they often do so through "membrane blebbing." During this unique process, an
|Contact: Bonnie Prescott|
Beth Israel Deaconess Medical Center