In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

Chondrocyte based regenerative therapies for intervertebral disc repair such as Autologous Disc Cell Transplantation (ADCT, CODON) and allogeneic juvenile chondrocyte implantation (NuQu®, ISTO Technologies) have demonstrated good outcomes in clinical trials. However concerns remain with the supply demand reconciliation and issues surrounding immunoreactivity which exist for allogeneic-type technologies. The use of stem cells is challenging due to high growth factor requirements, regulatory barriers and differentiation towards a stable phenotype. Therefore, there is a need to identify alternative non-disc cell sources for the development and clinical translation of next generation therapies for IVD regeneration. In this study, we compared Nasal Chondrocytes (NC) as a non-disc alternative chondrocyte source with Articular Chondrocytes (AC) in terms of cell yield, morphology, proliferation kinetics and ability to produce key extracellular matrix components under 5% and 20% oxygen conditions, with and without exogenous TGF-β supplementation. Results indicated that NC maintained proliferative capacity with high amounts of sGAG and lower collagen accumulation in the absence of TGF-β supplementation under 5% oxygen conditions. Importantly, osteogenesis and calcification was inhibited for NC when cultured in IVD-like microenvironmental conditions. The present study provides a rationale for the exploration of nasal chondrocytes as a promising, potent and clinically feasible autologous cell source for putative IVD repair strategies.