Effects of rAAV-Mediated Overexpression of sox9 and TGF-ß via Alginate Hydrogel-Guided Vector Delivery on the Chondroreparative Activities of Human Bone Marrow-Derived Mesenchymal Stromal Cells

IF 3.1 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Tissue Engineering and Regenerative Medicine Pub Date : 2023-08-18 DOI:10.1155/2023/4495697

Wei Liu, J. Venkatesan, Mahnaz Amini, T. Oláh, G. Schmitt, H. Madry, Magali Cucchiarini

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引用次数: 0

Abstract

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 sox9 and rAAV TGF-ß 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 sox9 and TGF-ß that significantly increases the proliferation and chondrogenic differentiation activities of the cells relative to control (marker lacZ) 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 (sox9 and TGF-ß) gene vectors to adeptly trigger the chondroreparative activities of hMSCs for future applications that aim at improving cartilage repair.

查看原文本刊更多论文

海藻酸盐水凝胶引导载体递送raav介导的sox9和TGF-ß过表达对人骨髓源间充质基质细胞软骨修复活性的影响

重组腺相关病毒（rAAV）载体在递送和过表达来自支持候选构建体受控释放的合适生物材料的治疗基因后，具有促进创伤软骨缺损和骨关节炎病变愈合的强大潜力。本工作的目的是检查通过藻酸盐水凝胶引导的载体递送给予软骨原性rAAV sox9和rAAV TGF-ß基因载体是否刺激人骨髓间充质基质细胞（hMSCs）的生物和软骨修复活性，作为未来植入软骨损伤部位的改良修复细胞的来源。随着时间的推移，使用藻酸盐（AlgPH155）水凝胶系统在hMSC中成功地实现了rAAV的递送（21 天），导致sox9和TGF-ß的有效过表达，其相对于对照（标记lacZ）基因转移显著增加细胞的增殖和软骨分化活性，同时有利地防止过早肥大、成骨和矿化。这项研究揭示了基于藻酸盐水凝胶的系统控制rAAV（sox9和TGF-ß）基因载体递送的潜力，以熟练地触发hMSCs的软骨修复活性，用于未来旨在改善软骨修复的应用。

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来源期刊

Journal of Tissue Engineering and Regenerative Medicine 生物-工程：生物医学

CiteScore

7.50

自引率

3.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.