Abstract
Human mesenchymal stem cells (hMSCs) show enormous potential in regenerative medicine and tissue engineering. However, current use of hMSCs in clinics is still limited because there is no appropriate way to control their behavior in vivo, such as differentiation to a desired cell type. Genetic modification may provide an opportunity to control the cells in an active manner. One of the major hurdles for genetic manipulation of hMSCs is the lack of an efficient and safe gene delivery system. Herein, biocompatible calcium phosphate (CaP)-based nanoparticles stabilized with a catechol-derivatized hyaluronic acid (dopa-HA) conjugate were used as a carrier for gene transfection to hMSCs for improved differentiation. Owing to the specific interactions between HA and CD44 of bone marrow-derived hMSCs, dopa-HA/CaP showed significantly higher transfection in hMSCs than branched polyethylenimine (bPEI, MW 25 kDa) with no cytotoxicity. The co-delivery of a plasmid DNA encoding bone morphogenetic protein 2 (BMP-2 pDNA) and micro RNA 148b (miRNA-148b) by dopa-HA/CaP achieved significantly improved osteogenic differentiation of hMSCs.
Highlights
Mesenchymal stem cells (MSCs) have the potential to differentiate into osteoblasts, adipocytes, myocytes, chondrocytes, and neuronal cells [1]
We showed that a conjugate of hyaluronic acid (HA) and 3,4-dihydroxy-L-phenylalanine, an unusual amino acid found in adherent threads of marine mussels, can effectively stabilize calcium phosphate (CaP) nanoparticles containing pDNA
Human mesenchymal stem cells derived from bone-marrow were purchased from Merck (SCC034, Burlington, MA, USA). hMSCs were seeded in a 96-well plate at a density of 7 × 103 cells/well and maintained in a DMEM medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin at 37 ◦ C in a humidified atmosphere of 5% CO2 . hMSCs within 7 to 8 passages were used
Summary
Mesenchymal stem cells (MSCs) have the potential to differentiate into osteoblasts, adipocytes, myocytes, chondrocytes, and neuronal cells [1]. BMP-2 provides an early-stage signal for osteogenic differentiation from mesenchymal progenitor cells [8,9,10,11]. It was originally identified by its ability to induce the formation of cartilage and bone [9,10,11,12]. Noggin plays an important role in the regulation of BMP-mediated differentiation by directly interacting with BMPs. Noggin and BMP interactions preclude BMPs from binding to their cell surface receptors and initiating signal transduction in cells. DNA encoding BMP-2 (pBMP-2) using dopa-HA/CaP could improve osteogenic differentiation of hMSCs in a synergistic manner by blocking the Noggin signal and stimulating differentiation at the same time
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