Authors:
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
Summary:
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.
Source:
Cell Reports; Vol. 10, Issue 8, 1261-1268 (03/03/15)