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

作者：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^*; Karp Jeffrey M

来源：Cell Reports, 2015, 10(8): 1261-1268.

DOI：10.1016/j.celrep.2015.01.057

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.

• 出版日期2015-3-3
• 单位MIT