Effective Remodelling of Human Osteoarthritic Cartilage by sox9 Gene Transfer and Overexpression upon Delivery of rAAV Vectors in Polymeric Micelles

Molecular Pharmaceutics
A Rey-RicoMagali Cucchiarini

Abstract

Recombinant adeno-associated virus (rAAV) vectors are well suited carriers to provide durable treatments for human osteoarthritis (OA). Controlled release of rAAV from polymeric micelles was already shown to increase both the stability and bioactivity of the vectors while overcoming barriers, precluding effective gene transfer. In the present study, we examined the convenience of delivering rAAV vectors via poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) polymeric (PEO-PPO-PEO) micelles to transfer and overexpress the transcription factor SOX9 in monolayers of human OA chondrocytes and in experimentally created human osteochondral defects. Human osteoarthritic (OA) chondrocytes and human osteochondral defect models were produced using human OA cartilage obtained from patients subjected to total knee arthroplasty. Samples were genetically modified by adding a rAAV-FLAG-h sox9 vector in its free form or via polymeric micelles for 10 days relative to control conditions (unmodified cells). The effects of sox9 overexpression in human OA cartilage samples were monitored by biochemical, histological, and immunohistochemical analyses. Delivery of rAAV-FLAG-h sox9 via polymeric micelles enhanced the levels of sox9 expression ...Continue Reading

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Citations

Aug 6, 2020·International Journal of Molecular Sciences·Dawid SzwedowskiJacek Kruczyński
Aug 16, 2019·Tissue Engineering and Regenerative Medicine·Jagadeesh Kumar VenkatesanMagali Cucchiarini
Oct 8, 2020·Biomaterials Science·Kübra Kaygisiz, Christopher V Synatschke
Feb 22, 2021·Drug Delivery and Translational Research·Héctor Rilo-AlvarezMarcos Garcia-Fuentes

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