Abstract
AbstractKnee cartilage does not regenerate spontaneously after injury, and a gold standard regenerative treatment algorithm has not been established. This study demonstrates preclinical safety and efficacy of scaffold-free, human juvenile cartilage-derived-chondrocyte (JCC) sheets produced from routine surgical discards using thermo-responsive cultureware. JCCs exhibit stable and high growth potential in vitro over passage 10, supporting possibilities for scale-up to mass production for commercialization. JCC sheets contain highly viable, densely packed cells, show no anchorage-independent cell growth, express mesenchymal surface markers, and lack MHC II expression. In nude rat focal osteochondral defect models, stable neocartilage formation was observed at 4 weeks by JCC sheet transplantation without abnormal tissue growth over 24 weeks in contrast to the nontreatment group showing no spontaneous cartilage repair. Regenerated cartilage was safranin-O positive, contained type II collagen, aggrecan, and human vimentin, and lacked type I collagen, indicating that the hyaline-like neocartilage formed originates from transplanted JCC sheets rather than host-derived cells. This study demonstrates the safety of JCC sheets and stable hyaline cartilage formation with engineered JCC sheets utilizing a sustainable tissue supply. Cost-benefit and scaling issues for sheet fabrication and use support feasibility of this JCC sheet strategy in clinical cartilage repair.
Funder
University Technology Acceleration Grant (UTAG) from the Utah Science, Technology, and Research (USTAR) program
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Developmental Biology,Biomedical Engineering,Medicine (miscellaneous)
Reference58 articles.
1. Huey, D. J., Hu, J. C. & Athanasiou, K. Unlike bone, cartilage regeneration remains elusive. Science 6933, 917–921 (2012).
2. Flanigan, D. C., Harris, J. D., Trinh, T. Q., Siston, R. A. & Brophy, R. H. Prevalence of chondral defects in Athletes’ Knees: A systematic review. Med. Sci. Sports Exerc. 42, 1795–1801 (2010).
3. Houck, D. A. et al. Do focal chondral defects of the knee increase the risk for progression to osteoarthritis? a review of the literature. Orthop. J. Sport. Med. 6, 1–8 (2018).
4. Minas, T. et al. Autologous chondrocyte implantation for joint preservation in patients with early osteoarthritis. Clin. Orthop. Relat. Res. 468, 147–157 (2010).
5. de Windt, T. S., Vonk, L. A., Brittberg, M. & Saris, D. B. F. Treatment and prevention of (early) osteoarthritis Using articular cartilage repair-fact or fiction? A Systematic Review. Cartilageo 4, 5S–12S (2013).
Cited by
14 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献