A small molecule screen for enhanced homing of systemically infused cells
| Autor: | Jidong Zhang, Oren Levy, Edward Han, Charles P. Lin, Jonathan Rothblatt, Luke J. Mortensen, Zijiang Yang, Brigitte Benhamou, Zhixiang Tong, Gerald Boquet, Juliet Musabeyezu, Jean-François Deleuze, Christelle Perrault, Jeffrey M. Karp, Tara Stratton, Marie-Christine Multon, Helia Safaee |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Karp, Jeffrey Michael |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Stromal cell Indoles Cell Intercellular Adhesion Molecule-1 CD11a Biology Mesenchymal Stem Cell Transplantation General Biochemistry Genetics and Molecular Biology Article Cell Line Maleimides Small Molecule Libraries 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Cell Movement medicine Cell Adhesion Animals Humans CD11a Antigen lcsh:QH301-705.5 Protein Kinase Inhibitors 030304 developmental biology Inflammation 0303 health sciences Microscopy Confocal Mesenchymal stem cell Mesenchymal Stem Cells 3. Good health Cell biology High-Throughput Screening Assays Up-Regulation Mice Inbred C57BL medicine.anatomical_structure lcsh:Biology (General) Cell culture 030220 oncology & carcinogenesis Homing (hematopoietic) |
| Zdroj: | Cell Reports, Vol 10, Iss 8, Pp 1261-1268 (2015) Elsevier |
| Popis: | 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. Sanofi Aventis (Firm) (Research Grant) National Institutes of Health (U.S.) (Grant HL095722) |
| Databáze: | OpenAIRE |
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