| Literature DB >> 25732817 |
Oren Levy1,2,3, Luke J Mortensen2,4, Gerald Boquet5, Zhixiang Tong1,2,3, Christelle Perrault5, Brigitte Benhamou5, Jidong Zhang5, Tara Stratton2,4, Edward Han1,2,3, Helia Safaee1,2,3, Juliet Musabeyezu1,2,3, Zijiang Yang1,2,3, Marie-Christine Multon5, Jonathan Rothblatt6, Jean-Francois Deleuze5, Charles P Lin2,4, Jeffrey M Karp1,2,3.
Abstract
Poor homing of systemically infused cells to disease sites may limit the success of exogenous cell-based therapy. In this study, we screened 9,000 signal-transduction modulators to identify hits that increase mesenchymal stromal cell (MSC) surface expression of homing ligands that bind to intercellular adhesion molecule 1 (ICAM-1), such as CD11a. Pretreatment of MSCs with Ro-31-8425, an identified hit from this screen, increased MSC firm adhesion to an ICAM-1-coated substrate in vitro and enabled targeted delivery of systemically administered MSCs to inflamed sites in vivo in a CD11a- (and other ICAM-1-binding domains)-dependent manner. This resulted in a heightened anti-inflammatory response. This represents a new strategy for engineering cell homing to enhance therapeutic efficacy and validates CD11a and ICAM-1 as potential targets. Altogether, this multi-step screening process may significantly improve clinical outcomes of cell-based therapies.Entities:
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Year: 2015 PMID： 25732817 PMCID： PMC4361231 DOI： 10.1016/j.celrep.2015.01.057
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423