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Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer
dc.contributor.author | Venkatesan, Jagadeesh Kumar | |
dc.contributor.author | Rey-Rico, Ana | |
dc.contributor.author | Meng, Weikun | |
dc.contributor.author | Schmitt, Gertrud | |
dc.contributor.author | Speicher-Mentges, Susanne | |
dc.contributor.author | Falentin-Daudré, Céline | |
dc.contributor.author | Leroux, Amélie | |
dc.contributor.author | Madry, Henning | |
dc.contributor.author | Migonney, Véronique | |
dc.contributor.author | Cucchiarini, Magali | |
dc.date.accessioned | 2024-07-10T14:17:14Z | |
dc.date.available | 2024-07-10T14:17:14Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Venkatesan, J.K.; Meng, W.; Rey-Rico, A.; Schmitt, G.; Speicher-Mentges, S.; Falentin-Daudré, C.; Leroux, A.; Madry, H.; Migonney, V.; Cucchiarini, M. Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer. Pharmaceutics 2020, 12, 280. https://doi.org/10.3390/pharmaceutics12030280 | es_ES |
dc.identifier.uri | http://hdl.handle.net/2183/37892 | |
dc.description.abstract | [Abstract] Background: The delivery of therapeutic genes in sites of articular cartilage lesions using non-invasive, scaffold-guided gene therapy procedures is a promising approach to stimulate cartilage repair while protecting the cargos from detrimental immune responses, particularly when targeting chondroreparative bone marrow-derived mesenchymal stromal cells in a natural microenvironment like marrow aspirates. Methods: Here, we evaluated the benefits of providing a sequence for the cartilage-specific sex-determining region Y-type high-mobility group box 9 (SOX9) transcription factor to human marrow aspirates via recombinant adeno-associated virus (rAAV) vectors delivered by poly(ε-caprolactone) (PCL) films functionalized via grafting with poly(sodium styrene sulfonate) (pNaSS) to enhance the marrow chondrogenic potential over time. Results: Effective sox9 overexpression was observed in aspirates treated with pNaSS-grafted or ungrafted PCL films coated with the candidate rAAV-FLAG-hsox9 (FLAG-tagged rAAV vector carrying a human sox9 gene sequence) vector for at least 21 days relative to other conditions (pNaSS-grafted and ungrafted PCL films without vector coating). Overexpression of sox9 via rAAV sox9/pNaSS-grafted or ungrafted PCL films led to increased biological and chondrogenic differentiation activities (matrix deposition) in the aspirates while containing premature osteogenesis and hypertrophy without impacting cell proliferation, with more potent effects noted when using pNaSS-grafted films. Conclusions: These findings show the benefits of targeting patients’ bone marrow via PCL film-guided therapeutic rAAV (sox9) delivery as an off-the-shelf system for future strategies to enhance cartilage repair in translational applications. | es_ES |
dc.description.sponsorship | Funding: This research was funded by a grant from the Deutsche Forschungsgemeinschaft (DFG VE 1099/1-1) and University Paris 13, Sorbonne Paris Cité. Acknowledgments: We thank R. J. Samulski (The Gene Therapy Center, University of North Carolina, Chapel Hill, NC), X. Xiao (The Gene Therapy Center, University of Pittsburgh, Pittsburgh, PA), G. Scherer (Institute for Human Genetics and Anthropology, Albert-Ludwig University, Freiburg, Germany) for the human sox9 cDNA, and E. F. Terwilliger (Division of Experimental Medicine, Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, MA) for providing the genomic AAV-2 plasmid clones and the 293 cell line. We acknowledge support by the Saarland University within the funding programme Open Access Publishing. | es_ES |
dc.description.sponsorship | Deutschland. Deutsche Forschungsgemeinschaft; DFG VE 1099/1-1 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation.uri | https://doi.org/10.3390/pharmaceutics12030280 | es_ES |
dc.rights | Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Cartilage repair | es_ES |
dc.subject | Human bone marrow aspirates | es_ES |
dc.subject | RAAV | es_ES |
dc.subject | SOX9 | es_ES |
dc.subject | PNaSS-grafted PCL films | es_ES |
dc.subject | Chondrogenesis | es_ES |
dc.title | Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Pharmaceutics | es_ES |
UDC.volume | 12(3) | es_ES |
UDC.issue | 280 | es_ES |
dc.identifier.doi | 10.3390/pharmaceutics12030280 |