Crosstalk Between Mesenchymal Stromal Cells and Chondrocytes: The Hidden Therapeutic Potential for Cartilage Regeneration.

Cartilage injuries following trauma create a puzzling clinical scenario. The finite reparative potential of articular cartilage is well known, and injuries are associated with an increased risk of osteoarthritis. Cell-based therapies have spotlighted chondrocytes and mesenchymal stromal cells (MSCs) as the functional unit of articular cartilage and the progenitor cells, respectively. The available clinical treatments cannot reproduce the biomechanical properties of articular cartilage and call for continuous investigations into alternative approaches. Co-cultures of chondrocytes and MSCs are an attractive in vitro system to step closer to the in vivo multicellular environment's complexity. Research on the mechanisms of interaction between both cell types will reveal essential cues to understand cartilage regeneration. This review describes the latest discoveries on these interactions, along with advantages and main challenges in vitro and in vivo. The successful clinical translation of in vitro studies requires establishing rigorous standards and clinically relevant research models and an organ-targeting therapeutic strategy.