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Titel: Remodeling of Human Osteochondral Defects via rAAV-Mediated Co-Overexpression of TGF-β and IGF-I from Implanted Human Bone Marrow-Derived Mesenchymal Stromal Cells
VerfasserIn: Morscheid, Stephanie
Venkatesan, Jagadeesh Kumar
Rey-Rico, Ana
Schmitt, Gertrud
Cucchiarini, Magali
Sprache: Englisch
Titel: Journal of Clinical Medicine
Bandnummer: 8
Heft: 9
Verlag/Plattform: MDPI
Erscheinungsjahr: 2019
Freie Schlagwörter: osteochondral defect repair
hMSCs
rAAV vectors
TGF-β
IGF-I
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: The application of chondrogenic gene sequences to human bone marrow-derived mesenchymal stromal cells (hMSCs) is an attractive strategy to activate the reparative activities of these cells as a means to enhance the processes of cartilage repair using indirect cell transplantation procedures that may improve the repopulation of cartilage lesions. In the present study, we examined the feasibility of co-delivering the highly competent transforming growth factor beta (TGF-β) with the insulin-like growth factor I (IGF-I) in hMSCs via recombinant adeno-associated virus (rAAV) vector-mediated gene transfer prior to implantation in a human model of osteochondral defect (OCD) ex vivo that provides a microenvironment similar to that of focal cartilage lesions. The successful co-overexpression of rAAV TGF-β/IGF-I in implanted hMSCs promoted the durable remodeling of tissue injury in human OCDs over a prolonged period of time (21 days) relative to individual gene transfer and the control (reporter lacZ gene) treatment, with enhanced levels of cell proliferation and matrix deposition (proteoglycans, type-II collagen) both in the lesions and at a distance, while hypertrophic, osteogenic, and catabolic processes could be advantageously delayed. These findings demonstrate the value of indirect, progenitor cell-based combined rAAV gene therapy to treat human focal cartilage defects in a natural environment as a basis for future clinical applications.
DOI der Erstveröffentlichung: 10.3390/jcm8091326
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-286892
hdl:20.500.11880/30013
http://dx.doi.org/10.22028/D291-28689
ISSN: 2077-0383
Datum des Eintrags: 13-Nov-2020
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Orthopädie
Professur: M - Prof. Dr. Henning Madry
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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