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001-es BibID:BIBFORM114717
035-os BibID:(WoS)000953912600001 (Scopus)85144755733
Első szerző:Schrenker, Steffen
Cím:In vivo rAAV-mediated human TGF-β overexpression reduces perifocal osteoarthritis and improves osteochondral repair in a large animal model at one year / S. Schrenker, M. Cucchiarini, L. Goebel, T. Olah, J. K. Venkatesan, G. Schmitt, S. Speicher-Mentges, J. Maihofer, L. Gao, D. Zurakowski, M. D. Menger, M. W. Laschke, H. Madry
Dátum:2023
ISSN:1063-4584
Megjegyzések:Objective: Osteoarthritis (OA) is a serious consequence of focal osteochondral defects. Gene transfer of human transforming growth factor beta (hTGF-β) with recombinant adeno-associated virus (rAAV) vectors offers a strategy to improve osteochondral repair. However, the long-term in vivo effects of such rAAV-mediated TGF-β overexpression including its potential benefits on OA development remain unknown. Method: Focal osteochondral defects in minipig knees received rAAV-lacZ (control) or rAAV-hTGF-β in vivo. After one year, osteochondral repair and perifocal OA were visualized using validated macroscopic scoring, ultra-high-field MRI at 9.4 T, and micro-CT. A quantitative estimation of the cellular densities and a validated semi-quantitative scoring of histological and immunohistological parameters completed the analysis of microarchitectural parameters. Results: Direct rAAV-hTGF-β application induced and maintained significantly improved defect filling and safranin O staining intensity and overall cartilage repair at one year in vivo. In addition, rAAV-hTGF-β led to significantly higher chondrocyte densities within the cartilaginous repair tissue without affecting chondrocyte hypertrophy and minimized subarticular trabecular separation. Of note, rAAV-hTGF-β significantly improved the adjacent cartilage structure and chondrocyte density and reduced overall perifocal OA development after one year in vivo. Conclusions: rAAV-hTGF-β treatment improves long-term osteochondral repair and delays the progression of perifocal OA in a translational model. These findings have considerable potential for targeted molecular approaches to treat focal osteochondral defects.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Osteochondral defects
Osteoarthritis
rAAV
Large animal model
Cartilage repair
TGF-β
Megjelenés:Osteoarthritis And Cartilage. - 31 : 4 (2023), p. 467-481. -
További szerzők:Cucchiarini, Magali Goebel, Lars Oláh Tamás (1983-) (élettanász) Venkatesan, Jagadeesh K. Schmitt, Gertrud Speicher-Mentges, Susanne Maihöfer, J. Gao, L. L. Zurakowski, D. Menger, Michael D. Laschke, Matthias W. Madry, Henning
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