State-of the-art and future perspective in co-culture systems for tendon engineering

Tendon is a connective tissue that links bone to muscle, allowing for maintenance of skeleton posture, joint movement, energy storage and transmission of muscle force to bone. Tendon is a hypocellular and hypovascular tissue of poor self-regeneration capacity. Current surgical treatments are of limited success, frequently resulting in reinjury. Upcoming cell therapies are primarily based on tenocytes, a cell population of limited self-renewal capacity in vitro or mesenchymal stromal cells, a cell population prone to ectopic bone formation in vivo. Over the years mono- or multi- factorial cell culture technologies have failed to effectively maintain tenocyte phenotype in culture during expansion or to prime mesenchymal stromal cells towards tenogenic lineage prior to implantation. Upon these limitations the concept of co-culture was conceived. Here, we comprehensively review and discuss tenogenic differentiation of mesenchymal stromal cells through direct or indirect culture with tenocytes in an attempt to generate a tenocyte or a tendon-like cell population for regenerative medicine purposes.