Please use this identifier to cite or link to this item: doi:10.22028/D291-30563
Title: Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer
Author(s): Venkatesan, Jagadeesh K.
Meng, Weikun
Rey-Rico, Ana
Schmitt, Gertrud
Speicher-Mentges, Susanne
Falentin-Daudré, Céline
Leroux, Amélie
Madry, Henning
Migonney, Véronique
Cucchiarini, Magali
Language: English
Title: Pharmaceutics
Volume: 12
Issue: 3
Publisher/Platform: MDPI
Year of Publication: 2020
Free key words: cartilage repair
human bone marrow aspirates
pNaSS-grafted PCL films
DDC notations: 610 Medicine and health
Publikation type: Journal Article
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.
DOI of the first publication: 10.3390/pharmaceutics12030280
Link to this record: urn:nbn:de:bsz:291--ds-305631
ISSN: 1999-4923
Date of registration: 27-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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