Chondrogenic Differentiation Processes in Human Bone-Marrow Aspirates Seeded in Three-Dimensional-Woven Poly(ɛ-Caprolactone) Scaffolds Enhanced by Recombinant Adeno-Associated Virus-Mediated SOX9 Gene Transfer.
Chondrogenic Differentiation Processes in Human Bone-Marrow Aspirates Seeded in Three-Dimensional-Woven Poly(ɛ-Caprolactone) Scaffolds Enhanced by Recombinant Adeno-Associated Virus-Mediated SOX9 Gene Transfer.
复制标题
重组腺相关病毒介导的 SOX9 基因转移增强三维编织聚己内酯支架中人骨髓抽吸物的软骨形成分化过程
DOI：
10.1089/hum.2017.165
复制
发表时间：
2018
影响因子：
4.2
通讯作者：
Cucchiarini M
中科院分区：
文献类型：
--
作者：
Venkatesan JK;Moutos FT;Rey-Rico A;Estes BT;Frisch J;Schmitt G;Madry H;Guilak F;Cucchiarini M
将基因治疗方法与组织工程程序相结合是有效治疗关节软骨病变的转化研究的活跃领域，特别是靶向软骨生成祖细胞，例如来自骨髓的那些。本研究评估了基因修饰浓缩的骨髓间充质干细胞诱导软骨形成的效果，通过重组腺相关病毒（rAAV）载体基因转移的性别决定区Y型高迁移率族蛋白9（SOX 9）因子接种在三维编织的聚（ε-己内酯; PCL）支架，提供模拟天然关节软骨的机械性能。据报道，在构建体中延长的有效SOX 9表达持续至少21天，这是评价的最长时间点，导致相对于对照条件（转基因或不存在载体处理）增强的代谢和软骨形成活性，但不影响样品中的增殖活性。rAAVSOX 9载体的应用还防止了种子浓缩物中不期望的肥大和终末分化。由于骨髓在手术过程中容易接近，因此这些发现揭示了在三维编织PCL支架内提供rAAV修饰的骨髓浓缩物用于修复局灶性软骨病变的治疗潜力。
Combining gene therapy approaches with tissue engineering procedures is an active area of translational research for the effective treatment of articular cartilage lesions, especially to target chondrogenic progenitor cells such as those derived from the bone marrow. This study evaluated the effect of genetically modifying concentrated human mesenchymal stem cells from bone marrow to induce chondrogenesis by recombinant adeno-associated virus (rAAV) vector gene transfer of the sex-determining region Y-type high-mobility group box 9 (SOX9) factor upon seeding in three-dimensional-woven poly(ɛ-caprolactone; PCL) scaffolds that provide mechanical properties mimicking those of native articular cartilage. Prolonged, effective SOX9 expression was reported in the constructs for at least 21 days, the longest time point evaluated, leading to enhanced metabolic and chondrogenic activities relative to the control conditions (reporterlacZgene transfer or absence of vector treatment) but without affecting the proliferative activities in the samples. The application of the rAAVSOX9vector also prevented undesirable hypertrophic and terminal differentiation in the seeded concentrates. As bone marrow is readily accessible during surgery, such findings reveal the therapeutic potential of providing rAAV-modified marrow concentrates within three-dimensional-woven PCL scaffolds for repair of focal cartilage lesions.
登录
查看更多内容
DOI：
10.1016/s0006-291x(02)03026-7
发表时间：
2003-02-07
影响因子：
3.1
作者：
Tsuchiya, H;Kitoh, H;Ishiguro, N
通讯作者：
Ishiguro, N
影响因子：
3.3
作者：
Wakitani, Shigeyuki;Mitsuoka, Tomoki;Horibe, Shuji
通讯作者：
Horibe, Shuji
对关节软骨修复未来的愿景。
影响因子：
3.1
作者：
M. Cucchiarini;H. Madry;F. Guilak;D. Saris;M. Stoddart;M. Wong;P. Roughley
通讯作者：
P. Roughley
用于关节软骨修复的细胞疗法。
DOI：
--
发表时间：
2005
期刊：
影响因子：
--
作者：
Abe Y;Pichika R;Aoki Y;An HS;Muehleman C;Kimura T;Masuda K;Sumiyoshi H et al.;Kimura T
通讯作者：
Kimura T
影响因子：
3.3
作者：
Wakitani, Shigeyuki;Okabe, Takahiro;Ohgushi, Hajime
通讯作者：
Ohgushi, Hajime