| Autor: |
Oren Levy, Luke J. Mortensen, Gerald Boquet, Zhixiang Tong, Christelle Perrault, Brigitte Benhamou, Jidong Zhang, Tara Stratton, Edward Han, Helia Safaee, Juliet Musabeyezu, Zijiang Yang, Marie-Christine Multon, Jonathan Rothblatt, Jean-Francois Deleuze, Charles P. Lin, Jeffrey M. Karp |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 10, Iss 8, Pp 1261-1268 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2015.01.057 |
| 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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