Human mesenchymal stem cells (hMSCs) show enormous potential in regenerative\nmedicine and tissue engineering. However, current use of hMSCs in clinics is still limited because\nthere is no appropriate way to control their behavior in vivo, such as differentiation to a desired\ncell type. Genetic modification may provide an opportunity to control the cells in an active manner.\nOne of the major hurdles for genetic manipulation of hMSCs is the lack of an effcient and safe gene\ndelivery system. Herein, biocompatible calcium phosphate (CaP)-based nanoparticles stabilized\nwith a catechol-derivatized hyaluronic acid (dopa-HA) conjugate were used as a carrier for gene\ntransfection to hMSCs for improved differentiation. Owing to the specific interactions between HA\nand CD44 of bone marrow-derived hMSCs, dopa-HA/CaP showed significantly higher transfection\nin hMSCs than branched polyethylenimine (bPEI, MW 25 kDa) with no cytotoxicity. The co-delivery\nof a plasmid DNA encoding bone morphogenetic protein 2 (BMP-2 pDNA) and micro RNA 148b\n(miRNA-148b) by dopa-HA/CaP achieved significantly improved osteogenic differentiation of hMSCs.
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