2014 Volume No 28 – pages 82-97
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Title: Induction of mesenchymal stem cell differentiation and cartilage formation by cross-linker-free collagen microspheres |
Author: M Mathieu, S Vigier, M-N Labour, C Jorgensen, E Belamie, D Noël |
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Address: Inserm U 844, Hôpital Saint-Eloi, INM, 80 Avenue Augustin Fliche, F-34091 Montpellier cedex 5, France |
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E-mail: marc.mathieu at inserm.fr |
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Key Words: Biomaterial, cartilage engineering, chondrogenesis, collagen, injectable, mesenchymal stem cell, microspheres, safety, self-assembly, transforming growth factor-β. |
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Publication date: September 2nd 2014 |
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Abstract: Because of poor self-healing ability, joint cartilage can undergo irreversible degradation in the course of various diseases or after injury. A promising approach for cartilage engineering consists of using of mesenchymal stem cells (MSC) and a differentiation factor combined with an injectable carrier biomaterial. We describe here a novel synthesis route for native collagen microspheres that does not involve the use of potentially toxic crosslinking agents. An emulsion was formed between a type I collagen solution and perfluorinated oil, stabilised by a biocompatible triblock perfluorinated copolymer surfactant. Spherical microparticles of fibrillar collagen were formed through a sol-gel transition induced by ammonia vapours. Electron microscopy observations showed that these self-cross-linked microspheres were constituted by a gel of striated collagen fibrils. Microspheres that were loaded with transforming growth factor beta (TGF-β)3 progressively released this differentiation factor over a four weeks period. Human MSC rapidly adhered to TGF-β3-loaded microspheres and, after 21 d of culture, exhibited typical chondrocyte morphology and produced an uncalcified matrix made of the predominant cartilage components, aggrecan and type II collagen, but devoid of the hypertrophic marker type X collagen. Subcutaneous co-injection of MSC and TGF-β3-loaded microspheres in mice consistently led to the formation of a cartilage-like tissue, which was however hypertrophic, calcified and vascularised. In conclusion, we developed cross-linker free collagen microspheres that allowed chondrogenic differentiation of MSC in vitro and in vivo. |
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Article download: Pages
82-97 (PDF file) |
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