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Study reveals insights that could aid in therapeutic use of mesenchymal stem cells
Date:11/15/2012

endothelial monolayers in the lab in ways that mimic the vascular barrier structure in the body and conduct dynamic high-resolution imaging studies of MSCs interacting with the endothelium under normal or inflamed conditions," explains Carman, an investigator in BIDMC's Center for Vascular Biology Research and Assistant Professor of Medicine at Harvard Medical School (HMS).

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
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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