Evolving concepts of chondrogenic differentiation: history, state-of-the-art and future perspectives.

As a cell source, multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs) are promising candidates for chondrogenic differentiation and subsequent cartilage regeneration. From previous literature, it is known that chondrogenic differentiation of MSCs inevitably leads to hypertrophy and subsequent endochondral ossification. In this review, we examine the history of currently established protocols of chondrogenic differentiation and elaborate on the roles of individual components of chondrogenic differentiation medium. We also summarise the effects of physical, chemical and biological factors involved, and propose potential strategies to differentiate MSCs into articular chondrocytes with homogenous mature phenotypes through spatial-temporal incorporation of cell differentiation and chondrogenesis.