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RGD and BMP-2 mimetic peptides crosstalk enhances osteogenic commitment of human bone marrow stem cells

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Plawinski, Laurent
Stone, E.
Durrieu, Marie-Christine
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Human bone marrow mesenchymal stem cells (hBMSCs) commitment and differentiation are dictated by bioactive molecules sequestered within their Extra Cellular Matrix (ECM). One common approach to mimic the physiological environment is to functionalize biomaterial surfaces with ECM-derived peptides able to recruit stem cells and trigger their linage-specific differentiation. The objective of this work was to investigate combinatorial effects of RGD and BMP-2 mimetic peptides on the osteogenic commitment of hBMSCs, without supplementing the media with pro-osteogenic factors. The RGD peptide promotes cell adhesion via cell transmembrane integrin receptors, while the BMP-2 peptide, corresponding to residues 73-92 of Bone Morphogenetic Protein-2, was shown to induce hBMSCs osteoblast differentiation. The immobilization of peptides on aminated glass was ascertained by X-ray Photoelectron Spectroscopy (XPS), the density of grafted peptides was quantified by fluorescence microscopy and the surface roughness was evaluated using Atomic Force Microscopy (AFM). The osteogenic commitment of hBMSCs cultured on RGD and/or BMP-2 surfaces was characterized by immunohistochemistry using STRO-1 as specific stem cells marker and Runx-2 as an earlier osteogenic marker. Biological results showed that the osteogenic commitment of hBMSCs was enhanced on bifunctionalized surfaces as compared to surfaces containing BMP-2, while on RGD surfaces cells mainly preserved their stemness character. These results demonstrated that RGD and BMP-2 mimetic peptides act synergistically to enhance hBMSCs osteogenesis without supplementing the media with osteogenic factors. These findings contribute to the development of biomimetic materials, allowing a deeper understanding of signaling pathways that govern the transition of stem cells towards the osteoblastic lineage.

Acta Biomaterialia, Vol. 36, 132–142 (2016)
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Stem cells , Biomimetic materials , Bone tissue engineering , Mimetic peptides , Surface modification
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article de recherche