Abstract
AbstractLocalized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.
Funder
U.S. Department of Defense
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Developmental Biology,Biomedical Engineering,Medicine (miscellaneous)
Reference72 articles.
1. C. Centers for Disease, Prevention. Prevalence and most common causes of disability among adults—United States, 2005. MMWR Morb. Mortal. Wkly. Rep. 58, 421–426 (2009).
2. Anderson, D. D. et al. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J. Orthop. Res. 29, 802–809 (2011).
3. Riedl, M., Vadala, G., Papalia, R. & Denaro, V. Three-dimensional, scaffold-free, autologous chondrocyte transplantation: a systematic review. Orthop. J. Sports Med. 8, 2325967120951152 (2020).
4. Tyyni, A. & Karlsson, J. Biological treatment of joint cartilage damage. Scand. J. Med. Sci. Sports 10, 249–265 (2000).
5. Freitag, J. et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen. Med. 14, 213–230 (2019).
Cited by
2 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