Stimulated Chondrogenesis via Chondrocytes Co-culturing

Abstract

It is well known that the intimate communication between different precursor cell populations leads to articular cartilage formation during joint development. Co-culture systems employing chondrocytes of divergent sources represent a promising approach to improve chondrogenesis of multi- or oligopotent cell types, such as mesenchymal stem cells of different origin, with putative applicability in articular cartilage repair. Osteoarthritic, dedifferentiated or non-articular (“heterotopic”) chondrocytes have been recruited for co-culturing with stem cells. However, the mode of direct cell-cell interactions and the exchange of soluble mediators, and the signaling pathways activated by co-culturing remain largely unexplored. This review summarises the available co-culture approaches that are utilised to improve chondrogenesis. The impact of different cell types, cell to cell ratios, direct or indirect, two- or three-dimensional culture conditions and techniques is analysed. Furthermore, the paracrine role of putative mediators of chondrogenesis, such as growth factors, cytokines, chemokines and cell-contact based interactions are discussed. Co-culture systems combining different multipotent cell types with chondrocytes can stimulate or stabilize chondrogenesis of progenitor cells, and vice-versa amplify chondrocyte proliferation. Growth factors, including Transforming Growth Factor (TGF)-β1, -β2, Insulin-like Growth Factor (IGF)-1 and Bone Morphogenic Protein (BMP)2 have been identified as soluble key mediators, improving chondrogenesis in co-culture. Other less characterised mediators, exchange mechanisms, and the formation of specialised direct cell-cell contacts may amplify chondrogenesis in co-culture. Further efforts should be undertaken to optimise chondrogenic co-culturing conditions by providing reduced oxygen tension and mechanostimulation, and to transfer the knowledge into in vivo models and the clinic.