Enhanced migratory activity and in vivo engraftment rate of human mesenchymal stem cells after microencapsulation in and transmigration through a collagen barrier

Abstract

Human mesenchymal stem cell (hMSC)-based therapies has extremely low engraftment rate. Strategies enhancing the migratory activities of these cells are critical to improving the engraftment rate and hence translational potential of MSC-based therapies. hMSCs are heterogeneous mixtures of multiple cell types, which are different in morphology, phenotype and functional properties including migratory activities. Here, we ask a question that whether hMSCs transmigrating through a collagen barrier have better migratory activities and in vivo engraftment rate. In brief, hMSCs were microencapsulated into reconstituted nano-fibrous collagen meshwork and allowed to transmigrate through this collagen barrier. Detailed investigations on the transmigrated MSCs including phenotype, proliferation, differentiation, migratory activity, integrin adhesion, MMP secretion and in vivo engraftment rate were conducted, in comparison with a number of control groups. Results showed that using a transwell assay, these transmigrated significantly enhanced migratory activities as compared to the controls, both in serum free medium and in medium containing major chemokines SDF-1 and Fractalkine for hMSCs. Among other mechanisms, the transmigrated hMSCs showed a dramatic increase in their contractility as measured by the traction force measured by a protein micropillar array-based traction force assay. Using a partial hepatectomy model in NOD/SCID mice, after tail vein injections of hMSCs, the transmigrated hMSC group showed a significantly higher engraftment rate comparing with the control group. Further nivestigations to delineate the detailed mechanism of contractility change is warranted.