Please use this identifier to cite or link to this item: doi:10.22028/D291-28003
Title: Therapeutic Effects of rAAV-Mediated Concomittant Gene Transfer and Overexpression of TGF-β and IGF-I on the Chondrogenesis of Human Bone-Marrow-Derived Mesenchymal Stem Cells
Author(s): Morscheid, Stephanie
Rey-Rico, Ana
Schmitt, Gertrud
Madry, Henning
Cucchiarini, Magali
Venkatesan, Jagadeesh Kumar
Language: English
Title: International Journal of Molecular Sciences
Volume: 20
Issue: 10
Publisher/Platform: MDPI
Year of Publication: 2019
Free key words: cartilage repair
rAAV vectors
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Application of chondroreparative gene vectors in cartilage defects is a powerful approach to directly stimulate the regenerative activities of bone-marrow-derived mesenchymal stem cells (MSCs) that repopulate such lesions. Here, we investigated the ability of combined recombinant adeno-associated virus (rAAV) vector-mediated delivery of the potent transforming growth factor beta (TGF-β) and insulin-like growth factor I (IGF-I) to enhance the processes of chondrogenic differentiation in human MSCs (hMSCs) relative to individual candidate treatments and to reporter (lacZ) gene condition. The rAAV-hTGF-β and rAAV-hIGF-I vectors were simultaneously provided to hMSC aggregate cultures (TGF-β/IGF-I condition) in chondrogenic medium over time (21 days) versus TGF-β/lacZ, IGF-I/lacZ, and lacZ treatments at equivalent vector doses. The cultures were then processed to monitor transgene (co)-overexpression, the levels of biological activities in the cells (cell proliferation, matrix synthesis), and the development of a chondrogenic versus osteogenic/hypertrophic phenotype. Effective, durable co-overexpression of TGF-β with IGF-I via rAAV enhanced the proliferative, anabolic, and chondrogenic activities in hMSCs versus lacZ treatment and reached levels that were higher than those achieved upon single candidate gene transfer, while osteogenic/hypertrophic differentiation was delayed over the period of time evaluated. These findings demonstrate the potential of manipulating multiple therapeutic rAAV vectors as a tool to directly target bone-marrow-derived MSCs in sites of focal cartilage defects and to locally enhance the endogenous processes of cartilage repair
DOI of the first publication: 10.3390/ijms20102591
Link to this record: urn:nbn:de:bsz:291--ds-280031
ISSN: 1422-0067
Date of registration: 12-Nov-2020
Faculty: M - Medizinische Fakultät
Department: M - Orthopädie
Professorship: M - Prof. Dr. Henning Madry
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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