Abstract
The repair of large cartilage defects with hyaline cartilage continues to be a challenging clinical issue. We recently reported that the forced expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) can induce chondrogenic cells from mouse dermal fibroblast culture without going through a pluripotent state. We here generated induced chondrogenic (iChon) cells from human dermal fibroblast (HDF) culture with the same factors. We developed a chondrocyte-specific COL11A2 promoter/enhancer lentiviral reporter vector to select iChon cells. The human iChon cells expressed marker genes for chondrocytes but not fibroblasts, and were derived from non-chondrogenic COL11A2-negative cells. The human iChon cells formed cartilage but not tumors in nude mice. This approach could lead to the preparation of cartilage directly from skin in human, without going through pluripotent stem cells.
Highlights
Articular cartilage provides shock absorption and lubrication in diarthrodial joints
These results suggest that forced expression of c-MYC, KLF4 and SOX9 can produce induced chondrogenic cells from human skin fibroblast cultures
Small articular cartilage defects measuring less than 2 cm2 in size can be treated with autologous chondrocyte transplantation, the treatment of larger cartilage defects remains a challenge
Summary
Articular cartilage provides shock absorption and lubrication in diarthrodial joints. Articular cartilage is a hyaline cartilage which consists of chondrocytes and cartilage extracellular matrix composed of types II, IX and XI collagen molecules, proteoglycans, and other matrix proteins. Cartilage damage sometimes heals with fibrocartilage, which differs from hyaline cartilage. As the presence of type I collagen impairs the development of cartilage-specific matrix architecture and mechanical function, the repair of cartilage damage by fibrocartilage results in morbidity and functional impairment. The goal for repair of cartilage injury is the regeneration of organized hyaline cartilage, rather than healing with fibrocartilage [3]. Defects larger than 4 cm in size cannot be repaired because of the lack of a sufficient number of bona fide chondrocytes to fill the defect
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