Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

Significance Despite significant efforts, stable and organized human cartilage has not been grown from human mesenchymal stem cells in vitro. We report the formation of organized cartilage discs that resemble the articular cartilage from self-assembling human mesenchymal stem cells by implementing spatiotemporal regulation in vitro that mimics native development. Selective application of chondrogenic and hypertrophic induction regimens enabled the maintenance of functional hyaline cartilage and progressive deep-zone mineralization. We demonstrate that this simple biomimetic approach helped mature the cartilage discs and enabled them to remain stable and organized following implantation. These findings highlight the limitations of current isotropic culture, and could greatly accelerate the development of new therapeutic modalities for cartilage repair from a patient’s own cells.