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Int. J. Mol. Sci. 2018, 19(9), 2635; https://doi.org/10.3390/ijms19092635

Improved Chondrogenic Differentiation of rAAV SOX9-Modified Human MSCs Seeded in Fibrin-Polyurethane Scaffolds in a Hydrodynamic Environment

1
Center of Experimental Orthopaedics, Saarland University, D-66421 Homburg/Saar, Germany
2
AO Research Institute Davos, 7270 Davos Platz, Switzerland
3
Department of Orthopaedic Surgery, Saarland University Medical Center and Saarland University, D-66421 Homburg/Saar, Germany
These authors contribute equally to this paper.
*
Author to whom correspondence should be addressed.
Received: 23 July 2018 / Revised: 30 August 2018 / Accepted: 3 September 2018 / Published: 5 September 2018
(This article belongs to the Special Issue Biological Basis of Musculoskeletal Regeneration)
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Abstract

The repair of focal articular cartilage defects remains a problem. Combining gene therapy with tissue engineering approaches using bone marrow-derived mesenchymal stem cells (MSCs) may allow the development of improved options for cartilage repair. Here, we examined whether a three-dimensional fibrin-polyurethane scaffold provides a favorable environment for the effective chondrogenic differentiation of human MSCs (hMSCs) overexpressing the cartilage-specific SOX9 transcription factor via recombinant adeno-associated virus (rAAV) -mediated gene transfer cultured in a hydrodynamic environment in vitro. Sustained SOX9 expression was noted in the constructs for at least 21 days, the longest time point evaluated. Such spatially defined SOX9 overexpression enhanced proliferative, metabolic, and chondrogenic activities compared with control (reporter lacZ gene transfer) treatment. Of further note, administration of the SOX9 vector was also capable of delaying premature hypertrophic and osteogenic differentiation in the constructs. This enhancement of chondrogenesis by spatially defined overexpression of human SOX9 demonstrate the potential benefits of using rAAV-modified hMSCs seeded in fibrin-polyurethane scaffolds as a promising approach for implantation in focal cartilage lesions to improve cartilage repair. View Full-Text
Keywords: cartilage repair; hMSCs; chondrogenesis; rAAV; SOX9; fibrin-polyurethane scaffolds; bioreactors cartilage repair; hMSCs; chondrogenesis; rAAV; SOX9; fibrin-polyurethane scaffolds; bioreactors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Venkatesan, J.K.; Gardner, O.; Rey-Rico, A.; Eglin, D.; Alini, M.; Stoddart, M.J.; Cucchiarini, M.; Madry, H. Improved Chondrogenic Differentiation of rAAV SOX9-Modified Human MSCs Seeded in Fibrin-Polyurethane Scaffolds in a Hydrodynamic Environment. Int. J. Mol. Sci. 2018, 19, 2635.

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