A small-molecule screen for enhanced homing of systemically infused cells.

Autor:	Levy O; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139., Mortensen LJ; Harvard Stem Cell Institute, Cambridge, MA 02139.; Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Boquet G; Sanofi R&D , Centre de recherche Vitry-Alfortville, 13 quai Jules Guesde, 94403 Vitry-sur-Seine Cédex, France., Tong Z; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139., Perrault C; Sanofi R&D , Centre de recherche Vitry-Alfortville, 13 quai Jules Guesde, 94403 Vitry-sur-Seine Cédex, France., Benhamou B; Sanofi R&D , Centre de recherche Vitry-Alfortville, 13 quai Jules Guesde, 94403 Vitry-sur-Seine Cédex, France., Zhang J; Sanofi R&D , Centre de recherche Vitry-Alfortville, 13 quai Jules Guesde, 94403 Vitry-sur-Seine Cédex, France., Stratton T; Harvard Stem Cell Institute, Cambridge, MA 02139.; Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Han E; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139., Safaee H; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139., Musabeyezu J; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139., Yang Z; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139., Multon MC; Sanofi R&D , Centre de recherche Vitry-Alfortville, 13 quai Jules Guesde, 94403 Vitry-sur-Seine Cédex, France., Rothblatt J; Sanofi R&D, 270 Albany Street, Cambridge, Massachusetts 02139, USA., Deleuze JF; Sanofi R&D , Centre de recherche Vitry-Alfortville, 13 quai Jules Guesde, 94403 Vitry-sur-Seine Cédex, France., Lin CP; Harvard Stem Cell Institute, Cambridge, MA 02139.; Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Karp JM; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.; Harvard Stem Cell Institute, Cambridge, MA 02139.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Mar 03; Vol. 10 (8), pp. 1261-1268. Date of Electronic Publication: 2015 Feb 26.
DOI:	10.1016/j.celrep.2015.01.057
Abstrakt:	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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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