Chondrocyte redifferentiation and its application in engineering chondrogenesis of synovial mesenchymal stem cells in co-culture systems

Abstract

Cartilage tissue degenerations and diseases are progressively increasing worldwide and threatening life qualities of human beings. Regeneration of cartilage tissue is difficult and challenging due to its avascular nature. Regenerative medicine, where damaged or lost tissues and organs are repaired or regenerated, has drawn more and more popular attentions compared to other traditional therapies. Specifically in cartilage tissue regeneration, autologous chondrocytes are isolated from the patient, amplified in vitro, seeded in a scaffold, and then transplanted back to the injured site. However, this ex vivo approach cannot provide sustained growth factors to the engineered tissue once it has been transplanted back into human bodies. There are also concerns over chondrocyte dedifferentiation during monolayer amplification, where functionally and mechanically undesirable type I collagen was automatically up-regulated. Delivery of TGF-β3 and Col I-suppressing shRNA transgenes was carried out to investigate Col I-suppressed redifferentiation of chondrocytes that have undergone dedifferentiation in monolayer culture. Effective redifferentiation was achieved in 3D alginate hydrogel culture, but the invasive gene delivery method would, to some degree, impose damages to the therapeutic cells, rendering detrimental side effects after transplantation. Co-culture system, where transgene transduced chondrocytes as companion cells were co-cultured to guide intact SMSCs as the therapeutic cells to chondrogenic pathways, was proposed and studied subsequently. This strategy takes advantages of SMSCs’ easy access, high proliferative capacity, and relative ease in induction for chondrogenesis, and meanwhile bypasses deficiencies in chondrocytes’ scarce source and dedifferentiation potential. Results showed successful induction on chondrogenic differentiation of SMSCs and the entire co-culture system.