Next Article in Journal
Synthesis and Characterization of Polyfumarateurethane Nanoparticles for Sustained Release of Bupivacaine
Previous Article in Journal
The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process
Open AccessArticle

Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer

1
Center of Experimental Orthopaedics, Saarland University Medical Center, D-66421 Homburg/Saar, Germany
2
LBPS/CSPBAT UMR CNRS 7244, Université Sorbonne Paris Nord, F-93430 Villetaneuse, France
3
Department of Orthopaedic Surgery, Saarland University Medical Center, D-66421 Homburg/Saar, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(3), 280; https://doi.org/10.3390/pharmaceutics12030280
Received: 15 January 2020 / Revised: 13 March 2020 / Accepted: 19 March 2020 / Published: 21 March 2020
(This article belongs to the Special Issue Scaffold-Mediated Gene Delivery)
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. View Full-Text
Keywords: cartilage repair; human bone marrow aspirates; rAAV; SOX9; pNaSS-grafted PCL films; chondrogenesis cartilage repair; human bone marrow aspirates; rAAV; SOX9; pNaSS-grafted PCL films; chondrogenesis
Show Figures

Graphical abstract

MDPI and ACS Style

Venkatesan, J.K.; Meng, W.; Rey-Rico, A.; Schmitt, G.; Speicher-Mentges, S.; Falentin-Daudré, C.; Leroux, A.; Madry, H.; Migonney, V.; Cucchiarini, M. Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer. Pharmaceutics 2020, 12, 280.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop