A Small-Molecule Screen for Enhanced Homing of Systemically Infused Cells
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Levy-2015-A small-molecule scr.pdf
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Author(s)
Levy, Oren
Mortensen, Luke J.
Boquet, Gerald
Tong, Zhixiang
Perrault, Christelle
Benhamou, Brigitte
Zhang, Jidong
Stratton, Tara
Han, Edward
Safaee, Helia
Date Issued
February 2015
Journal
Cell Reports
Publisher
Elsevier
Citation
Levy, Oren, Luke J. Mortensen, Gerald Boquet, Zhixiang Tong, Christelle Perrault, Brigitte Benhamou, Jidong Zhang, et al. “A Small-Molecule Screen for Enhanced Homing of Systemically Infused Cells.” Cell Reports 10, no. 8 (March 2015): 1261–1268.
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2015.01.057
