Cell therapy: Showing cells the way home

Abstract

The clinical potential of cell-based therapies is limited by poor targeting of systemically infused cells to diseased tissues. In our recent study, we have developed a multi-step screening platform to identify small molecules that boost the homing properties of mesenchymal stem cells (MSCs) to sites of inflammation. First, a medium-throughput screen was designed to identify small molecules that upregulate surface expression of the homing integrin, cd11a (integrin αL). Ro-31-8425, a kinase inhibitor, was identified as the most potent inducer of cd11a surface expression, and was also shown to significantly increase MSC firm adhesion to the endothelial ligand of cd11a, ICAM-1, using a microfluidics-based firm adhesion assay. Finally, systemically infused Ro-31-8425-pretreated MSCs displayed improved homing to sites of inflammation and a superior anti-inflammatory impact in a murine ear inflammation model.