Vedicherla S, Buckley C T
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; School of Medicine, Trinity College Dublin, Ireland.
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; School of Medicine, Trinity College Dublin, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, Royal College of Surgeons in Ireland & Trinity College Dublin, Ireland.
Tissue Cell. 2017 Aug;49(4):503-513. doi: 10.1016/j.tice.2017.05.002. Epub 2017 May 8.
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.
基于软骨细胞的椎间盘修复再生疗法，如自体椎间盘细胞移植（ADCT，Codon）和同种异体幼年软骨细胞植入（NuQu，ISTO Technologies），已在临床试验中显示出良好的效果。然而，对于同种异体技术而言，供需协调以及免疫反应相关问题仍然令人担忧。由于对生长因子的高需求、监管障碍以及向稳定表型的分化，干细胞的应用具有挑战性。因此，有必要为下一代椎间盘再生疗法的开发和临床转化确定替代的非椎间盘细胞来源。在本研究中，我们比较了鼻软骨细胞（NC）作为一种非椎间盘替代软骨细胞来源与关节软骨细胞（AC）在细胞产量、形态、增殖动力学以及在5%和20%氧气条件下，添加和不添加外源性转化生长因子-β（TGF-β）时产生关键细胞外基质成分的能力。结果表明，在5%氧气条件下不添加TGF-β时，鼻软骨细胞保持增殖能力，产生大量硫酸糖胺聚糖（sGAG）且胶原蛋白积累较少。重要的是，当在类似椎间盘的微环境条件下培养时，鼻软骨细胞的成骨和钙化受到抑制。本研究为探索鼻软骨细胞作为一种有前景、有效且临床可行的自体细胞来源用于假定的椎间盘修复策略提供了理论依据。
