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 [1]. 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 [2]. 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 [3]. 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.
Using small molecule pretreatment to control cell behavior post-infusion possesses multiple advantages over other bioengineering approaches, such as chemical surface modification or DNA engineering. Small molecule-induced transient modification of signaling pathways offers a potentially safe, simple, cost-effective and highly scalable approach. Moreover, the described versatile multi-step screening platform can be readily tweaked to potentially target virtually any cell type to multiple sites in the body. This platform consists of four essential steps: i) Screening…
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