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

MSC uses hydrostatic pressure to create a bulge or bleb in the cell's outer membrane that exerts mechanical force against the endothelium, leading to the initial break in its barrier that initiates transmigration. "We demonstrated that MSCs can transmigrate between endothelial cellscalled paracellular transmigrationand directly through a single endothelial cellcalled transcellular migration," says Karp. "This is an exciting finding as it provides a new axis that potentially can be modulated for developing next-generation MSC therapy." During transcelluar migration, an MSC doesn't actually enter an endothelial cell, but rather forms a pore through which it then migrates.

Interestingly, say the researchers, these findings may also provide insights on how some tumor cells spread or metastasize, as migratory blebbing has been observed in a number of embryonic germ cells and in some tumor cells. "Our finding shows for the first time that blebbing may function in the critical barrier-breaching event of MSC migration through endothelial cells," says Carman. "This suggests that blebs could similarly function in cancer invasiveness."

For now, however, Carman and his colleagues will focus on MSCs. Among their next steps is to verify that the results generated in the lab hold true within the body. "From there, we wish to iterate back and forth between our in vitro and in vivo systems to explore a range of bioengineering approaches that build on the new knowledge from this study to design improved delivery and efficacy of MSC therapeutics," says Carman, adding that as the understanding of the mechanisms of MSC movement grows, researchers' abilities to enhance homing to specific tissues through engineered approaches should help bring MSC therapy closer to the clinic.


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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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