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

Abstract

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.

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

“…This has motivated many researchers into identifying and characterizing alternative cell sources for disc regeneration, which is a key step towards translating therapies into clinical practice . Primary, differentiated cells from other skeletal sites with reduced risk for donor site morbidity, such as articular and nasal cartilage, have been investigated in vitro and in animal models for NP regeneration . While these cell types do exhibit some phenotypic differences to native NP cells, their relative ease of isolation, differentiated state and higher propensity to deposit extracellular matrix may make them attractive alternatives in the future and warrant further consideration and exploration.…”

Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

“…Its main role is to regulate dynamic equilibrium of ECM, including various collagenases and elastases incorporated in the matrix and integrated in the plasma membrane [ 27 ]. The synthesis and decomposition of normal intervertebral disc matrix maintain a balance, and its decomposition is mainly through the generation and activation of catabolic enzymes, including MMPs and a disintegrin and metalloproteinase [ 28 ]. The degradation of the matrix is in equilibrium with the synthesis of the new matrix [ 28 ].…”

“…The synthesis and decomposition of normal intervertebral disc matrix maintain a balance, and its decomposition is mainly through the generation and activation of catabolic enzymes, including MMPs and a disintegrin and metalloproteinase [ 28 ]. The degradation of the matrix is in equilibrium with the synthesis of the new matrix [ 28 ]. Bone morphogenetic protein-2 (BMP-2), insulin-like growth factor-1, BMP-7 (also known as osteogenic protein-1), growth differentiation factor 5, and transforming growth factor- β can stimulate the synthesis of matrix [ 29 ].…”

Promise, progress, and problems in whole disc tissue engineering

“…Other differentiated cell types such as articular chondrocytes have also been used in whole disc tissue engineering, but only for the NP region, and similar limitations exist in obtaining these cells with respect to donor site morbidity . Nasal chondrocytes may be a promising alternate cell source for tissue engineering of the NP region, as it has been shown that they maintain their proliferative and matrix production capacity even in a simulated disc‐like microenvironment in vitro …”

“…44,47 Nasal chondrocytes may be a promising alternate cell source for tissue engineering of the NP region, as it has been shown that they maintain their proliferative and matrix production capacity even in a simulated disc-like microenvironment in vitro. 96 As an alternative to native disc cells, autologous or allogeneic…”