Please use this identifier to cite or link to this item: doi:10.22028/D291-44203
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Title: Effects of TGF-β Overexpression via rAAV Gene Transfer on the Early Repair Processes in an Osteochondral Defect Model in Minipigs
Author(s): Cucchiarini, Magali
Asen, Ann-Kathrin
Goebel, Lars
Venkatesan, Jagadeesh K.
Schmitt, Gertrud
Zurakowski, David
Menger, Michael D.
Laschke, Matthias W.
Madry, Henning
Language: English
Title: The American Journal of Sports Medicine
Volume: 46
Issue: 8
Pages: 1987-1996
Publisher/Platform: Sage
Year of Publication: 2018
Free key words: osteochondral defects
minipigs
cartilage repair
rAAV
TGF-b
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Background: Application of the chondrogenic transforming growth factor beta (TGF-b) is an attractive approach to enhance the intrinsic biological activities in damaged articular cartilage, especially when using direct gene transfer strategies based on the clinically relevant recombinant adeno-associated viral (rAAV) vectors. Purpose: To evaluate the ability of an rAAV–TGF-b construct to modulate the early repair processes in sites of focal cartilage injury in minipigs in vivo relative to control (reporter lacZ gene) vector treatment. Study Design: Controlled laboratory study. Methods: Direct administration of the candidate rAAV–human TGF-b (hTGF-b) vector was performed in osteochondral defects created in the knee joint of adult minipigs for macroscopic, histological, immunohistochemical, histomorphometric, and micro– computed tomography analyses after 4 weeks relative to control (rAAV-lacZ) gene transfer. Results: Successful overexpression of TGF-b via rAAV at this time point and in the conditions applied here triggered the cellular and metabolic activities within the lesions relative to lacZ gene transfer but, at the same time, led to a noticeable production of type I and X collagen without further buildup on the subchondral bone. Conclusion: Gene therapy via direct, local rAAV–hTGF-b injection stimulates the early reparative activities in focal cartilage lesions in vivo. Clinical Relevance: Local delivery of therapeutic (TGF-b) rAAV vectors in focal defects may provide new, off-the-shelf treatments for cartilage repair in patients in the near future.
DOI of the first publication: 10.1177/0363546518773709
URL of the first publication: https://doi.org/10.1177/0363546518773709
Link to this record: urn:nbn:de:bsz:291--ds-442031
hdl:20.500.11880/39517
http://dx.doi.org/10.22028/D291-44203
ISSN: 1552-3365
0363-5465
Date of registration: 29-Jan-2025
Faculty: M - Medizinische Fakultät
Department: M - Chirurgie
M - Orthopädie
Professorship: M - Prof. Dr. Henning Madry
M - Prof. Dr. Michael D. Menger
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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