engleski

Gene therapy in articular cartilage repair

Gene therapy in articular cartilage repair. The restoration of damaged articular cartilage remains one of the biggest challenges in modern clinical orthopaedics. There is no pharmacological treatment that promotes the repair of cartilage, and non-operative treatment inevitably leads to the development of premature osteoarthritis. Current treatment modalities include microfracture, transplantation of osteochondral grafts and autologous chondrocyte implantation (ACI), each having its own benefits and shortcomings. New biological approaches to cartilage repair that are based on the use of cells and molecules that promote chondrogenesis and/or inhibit cartilage breakdown offer a promising alternative to current treatment options. Chondrogenesis is a precisely orchestrated process which involves many growth factors and signaling molecules, and by modifying the local cellular environment, it is possible to enhance formation of more natural cartilage tissue within the defect. These bioactive molecules are difficult to administer effectively. For those that are proteins or RNA molecules, gene transfer has emerged as an attractive option for their sustained synthesis at the site of repair. To accomplish this task, two main strategies have been explored. The direct or in vivo approach delivers exogenous DNA directly into the joint. In this case synovial lining cells are the main site of gene transfer ; depending on the vector, cells around or within the defect may also be genetically modified. During indirect or ex vivo delivery, cells are recovered, genetically manipulated outside the body, and then returned to the defect. Delivery of the genetic material to the living cell can be accomplished by use of either viral or non- viral vectors. While viral vectors are much more effective, they raise several safety concerns. Numerous preclinical animal studies have confirmed the effectiveness of these approaches in joints, and several phase I and II clinical gene therapy studies in the local treatment of arthritis provide reason for cautious optimism. This chapter will provide insight into the field of gene therapy in cartilage repair, and its potential for safe and effective clinical translation.

cartilage defects, gene therapy, vectors, growth factors

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