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A Small-Molecule Screen for Enhanced Homing of Systemically Infused Cells

Authors :
Harvard University--MIT Division of Health Sciences and Technology
Karp, Jeffrey Michael
Levy, Oren
Mortensen, Luke J.
Boquet, Gerald
Tong, Zhixiang
Perrault, Christelle
Benhamou, Brigitte
Zhang, Jidong
Stratton, Tara
Han, Edward
Safaee, Helia
Musabeyezu, Juliet
Yang, Zijiang
Multon, Marie-Christine
Rothblatt, Jonathan
Deleuze, Jean-Francois
Lin, Charles P.
Harvard University--MIT Division of Health Sciences and Technology
Karp, Jeffrey Michael
Levy, Oren
Mortensen, Luke J.
Boquet, Gerald
Tong, Zhixiang
Perrault, Christelle
Benhamou, Brigitte
Zhang, Jidong
Stratton, Tara
Han, Edward
Safaee, Helia
Musabeyezu, Juliet
Yang, Zijiang
Multon, Marie-Christine
Rothblatt, Jonathan
Deleuze, Jean-Francois
Lin, Charles P.
Source :
Elsevier
Publication Year :
2016

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.<br />Sanofi Aventis (Firm) (Research Grant)<br />National Institutes of Health (U.S.) (Grant HL095722)

Details

Database :
OAIster
Journal :
Elsevier
Notes :
application/pdf, en_US
Publication Type :
Electronic Resource
Accession number :
edsoai.on1155491009
Document Type :
Electronic Resource