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Significance The study offers a pharmacological solution to the challenging target of inducing stable chondrogenesis by human mesenchymal stromal cells (hMSCs), including protection against vascularization. Cells were reversed from the tendency to follow the default differentiation pathway, namely endochondral ossification and osteogenesis. Our findings open perspectives in articular cartilage regeneration, as well as in the establishment of hMSC-based models of cartilage development, physiology, and possibly pathology. Importantly, the results were achieved by mimicking molecular processes occurring during embryonic cartilage formation. This indicates that adult hMSCs share similarities with embryonic mesenchyme and validates the relevance to engineer developmental processes (“developmental engineering”) to control fate specification by adult stem/progenitor cell systems.

Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis