Ex vivo gene therapy approaches to cartilage repair☆

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Degeneration of articular cartilage is one of the great clinical challenges that still lack a convincing therapeutic solution. Traumatically induced lesions and final stages of osteoarthritis with substantial loss of cartilage tissue require the generation of new hyaline cartilage, because significant endogenous repair does not occur. Current joint-preserving surgical approaches, however, mostly lead to fibrous repair tissue that is rapidly degraded. In experimental studies, several differentiation factors have been shown to stimulate chondrogenesis, promoting the formation of functionally acceptable cartilage-like repair tissue. Cell-mediated transfer of the respective genes may ideally combine the supply of a chondrogenic cell population with the production of such factors directly at the site of the lesion. The treatment of earlier disease stages aims both at the protection of the remaining cartilage from further degradation and a stimulation of cartilage anabolism. Various studies proved the administration of anti-catabolic or anti-inflammatory cytokines into joints affected by cartilage destruction to be beneficial. However, the clinical utility of intraarticular protein application is limited by the short half-lives of such proteins in vivo. The transfer of cells over-expressing the respective genes may provide a more sustained delivery of the therapeutic molecules and thus be the more economic option.

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