ArticleJournal of experimental orthopaedics2017
Impact of mechanical stimulation on the chondrogenic processes in human bone marrow aspirates modified to overexpress sox9 via rAAV vectors.
Article in Journal of experimental orthopaedics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Overcoming challenges in cartilage regeneration: The role of chondrogenic inducers.Bioengineering & translational medicine · 2026Review
- Targeted chondrogenic differentiation of human MSCs using niosomes for SOX9 gene delivery: comparison of minicircle and conventional plasmids.Stem cell research & therapy · 2025Article
- Cartilage tissue engineering using decellularized biomatrix hydrogel containing TGF-β-loaded alginate microspheres in mechanically loaded bioreactor.Scientific reports · 2024Article
- Ultrasonic Enhancement of Chondrogenesis in Mesenchymal Stem Cells by Bolt-Clamped Langevin Transducers.Micromachines · 2023Article
- Chondrogenic Differentiation of Human Mesenchymal Stem Cells via SOX9 Delivery in Cationic Niosomes.Pharmaceutics · 2022Article
- Therapeutic Delivery of rAAVNanomaterials (Basel, Switzerland) · 2020Article
- Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy.Pharmaceutics · 2020Article
- Where is human-based cellular pharmaceutical R&D taking us in cartilage regeneration?3 Biotech · 2020Review
- The Role of Gene Therapy in Cartilage Repair.The archives of bone and joint surgery · 2019Review
- Tendon tissue engineering: An overview of biologics to promote tendon healing and repair.Journal of tissue engineeringReview
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEvaluation of gene-based approaches to target human bone marrow aspirates in conditions of mechanical stimulation that aim at reproducing the natural joint environment may allow to develop improved treatments for articular cartilage injuries. In the present study, we investigated the potential of rAAV-mediated sox9 gene transfer to enhance the chondrogenic differentiation processes in human bone marrow aspirates under established hydrodynamic conditions compared with the more commonly employed static culture conditions.
methodsFresh human bone marrow aspirates were transduced with rAAV-FLAG-hsox9 (40 μl) and maintained for up to 28 days in chondrogenic medium under mechanically-induced conditions in dynamic flow rotating bioreactors that permit tissue growth and matrix deposition relative to static culture conditions. The samples were then processed to examine the potential effects of sox9 overexpression on the cellular activities (matrix synthesis, proliferation) and on the chondrogenic differentiation potency compared with control treatments (absence of rAAV vector; reporter rAAV-lacZ, rAAV-RFP, and rAAV-luc gene transfer).
resultsProlonged, significant sox9 overexpression via rAAV was achieved in the aspirates for at least 28 days when applying the rAAV-FLAG-hsox9 construct, leading to higher, prolonged levels of matrix biosynthesis and to enhanced chondrogenic activities relative to control treatments especially when maintaining the samples under mechanical stimulation. Administration of sox9 however did not impact the indices of proliferation in the aspirates. Remarkably, sox9 gene transfer also durably delayed hypertrophic and osteogenic differentiation in the samples regardless of the conditions of culture applied versus control treatments.
conclusionsThe current observations show the value of genetically modifying human bone marrow aspirates upon mechanical stimulation by rAAV sox9 as a promising strategy for future treatments to improve cartilage repair by implantation in lesions where the tissue is submitted to natural mechanical forces.
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