Cell-based articular cartilage repair: the link between development and regeneration

SummaryClinical efforts to repair damaged articular cartilage (AC) currently face major obstacles due to limited intrinsic repair capacity of the tissue and unsuccessful biological interventions. This highlights a need for better therapeutic strategies. This review summarizes the recent advances in the field of cell-based AC repair. In both animals and humans, AC defects that penetrate into the subchondral bone marrow are mainly filled with fibrocartilaginous tissue through the differentiation of bone marrow mesenchymal stem cells (MSCs), followed by degeneration of repaired cartilage and osteoarthritis (OA). Cell therapy and tissue engineering techniques using culture-expanded chondrocytes, bone marrow MSCs, or pluripotent stem cells with chondroinductive growth factors may generate cartilaginous tissue in AC defects but do not form hyaline cartilage-based articular surface because repair cells often lose chondrogenic activity or result in chondrocyte hypertrophy. The new evidence that AC and synovium develop from the same pool of precursors with similar gene profiles and that synovium-derived chondrocytes have stable chondrogenic activity has promoted use of synovium as a new cell source for AC repair. The recent finding that NFAT1 and NFAT2 transcription factors (TFs) inhibit chondrocyte hypertrophy and maintain metabolic balance in AC is a significant advance in the field of AC repair. The use of synovial MSCs and discovery of upstream transcriptional regulators that help maintain the AC phenotype have opened new avenues to improve the outcome of AC regeneration