Liu Wei, Venkatesan Jagadeesh K, Amini Mahnaz, Oláh Tamás, Schmitt Gertrud, Madry Henning, Cucchiarini Magali
Center of Experimental Orthopaedics, Saarland University and Saarland University Medical Center, Homburg/Saar, Germany.
J Tissue Eng Regen Med. 2023 Aug 18;2023:4495697. doi: 10.1155/2023/4495697. eCollection 2023.
Recombinant adeno-associated virus (rAAV) vectors have a strong potential to promote the healing of traumatic cartilage defects and osteoarthritic lesions upon delivery and overexpression of therapeutic genes from suitable biomaterials that support a controlled release of the candidate constructs. The goal of the present work is to examine whether the administration of chondrogenic rAAV and rAAV TGF- gene vehicles via alginate hydrogel-guided vector delivery stimulates the biological and chondroreparative activities of human bone marrow-derived mesenchymal stromal cells (hMSCs) as a source of improved reparative cells for future implantation in sites of cartilage damage. The delivery of rAAV using an alginate (AlgPH155) hydrogel system is successfully achieved in hMSCs over time (21 days), leading to the effective overexpression of and TGF- that significantly increases the proliferation and chondrogenic differentiation activities of the cells relative to control (marker ) gene transfer while advantageously preventing premature hypertrophy, osteogenesis, and mineralization. This study reveals the potential of alginate hydrogel-based systems to control the delivery of rAAV ( and TGF-) gene vectors to adeptly trigger the chondroreparative activities of hMSCs for future applications that aim at improving cartilage repair.
重组腺相关病毒（rAAV）载体在通过支持候选构建体控释的合适生物材料递送和过表达治疗性基因时，具有促进创伤性软骨缺损和骨关节炎损伤愈合的强大潜力。本研究的目的是检验通过藻酸盐水凝胶引导载体递送软骨生成性rAAV和rAAV TGF-基因载体，是否能刺激人骨髓间充质基质细胞（hMSCs）的生物学和软骨修复活性，hMSCs可作为未来植入软骨损伤部位的改良修复细胞来源。随着时间推移（21天），在hMSCs中成功实现了使用藻酸盐（AlgPH155）水凝胶系统递送rAAV，导致 和TGF-有效过表达，相对于对照（标记 ）基因转移，显著增加了细胞的增殖和软骨生成分化活性，同时有利地防止了过早肥大、骨生成和矿化。本研究揭示了基于藻酸盐水凝胶的系统控制rAAV（ 和TGF-）基因载体递送以巧妙触发hMSCs软骨修复活性的潜力，用于未来旨在改善软骨修复的应用。
