Enhanced chondrogenic differentiation of induced pluripotent stem cells derived from human articular cartilage

INTRODUCTION: Acute impact-induced joint trauma often affects young and middleaged adults and significantly increases the risk of developing posttraumatic osteoarthritis. Since joint replacement surgery is not a realistic option for young individuals, there is a need for the development of alternative therapies to treat large cartilage defects. Because of their unlimited self-renewal, developmental plasticity and limited immunogenic potential, human induced pluripotent stem cells (hiPSC) represent an alternative source of patient-specific cells for cartilage regeneration. However, restricting hiPSC differentiation to articular-like chondrocytes, while inhibiting their maturation, poses a significant challenge. Our goal is to establish the molecular cues that control and restrict hiPSC chondrocyte differentiation and their use as a novel cellbased approach for articular cartilage repair. We propose that commitment of hiPSC to an articular-like chondrocyte phenotype is influenced by (i) the responsiveness of progenitor cells to chondrogenic factors; and (ii) the tissue source used for reprogrammed cells. We generated hiPSCs from human dermal fibroblasts and articular chondrocytes (hAC) to examine whether cartilage-derived hiPSCs exhibit superior chondrogenic potential to that of fibroblast-derived hiPSCs.