Department of Physiology, Christian Medical College, Vellore, India.
Centre for Stem Cell Research, (A Unit of InStem, Bengaluru), Christian Medical College, Vellore, India.
Sci Rep. 2021 Dec 8;11(1):23685. doi: 10.1038/s41598-021-03082-5.
Cell-based therapy for articular hyaline cartilage regeneration predominantly involves the use of mesenchymal stem cells and chondrocytes. However, the regenerated repair tissue is suboptimal due to the formation of mixed hyaline and fibrocartilage, resulting in inferior long-term functional outcomes. Current preclinical research points towards the potential use of cartilage-derived chondroprogenitors as a viable option for cartilage healing. Fibronectin adhesion assay-derived chondroprogenitors (FAA-CP) and migratory chondroprogenitors (MCP) exhibit features suitable for neocartilage formation but are isolated using distinct protocols. In order to assess superiority between the two cell groups, this study was the first attempt to compare human FAA-CPs with MCPs in normoxic and hypoxic culture conditions, investigating their growth characteristics, surface marker profile and trilineage potency. Their chondrogenic potential was assessed using mRNA expression for markers of chondrogenesis and hypertrophy, glycosaminoglycan content (GAG), and histological staining. MCPs displayed lower levels of hypertrophy markers (RUNX2 and COL1A1), with normoxia-MCP exhibiting significantly higher levels of chondrogenic markers (Aggrecan and COL2A1/COL1A1 ratio), thus showing superior potential towards cartilage repair. Upon chondrogenic induction, normoxia-MCPs also showed significantly higher levels of GAG/DNA with stronger staining. Focused research using MCPs is required as they can be suitable contenders for the generation of hyaline-like repair tissue.
基于细胞的关节透明软骨再生治疗主要涉及间充质干细胞和软骨细胞的应用。然而,由于形成混合透明软骨和纤维软骨,再生修复组织不理想,导致长期功能结果较差。目前的临床前研究表明,软骨来源的软骨祖细胞作为一种可行的软骨愈合选择。纤维连接蛋白黏附试验衍生的软骨祖细胞(FAA-CP)和迁移软骨祖细胞(MCP)表现出适合新软骨形成的特征,但它们是通过不同的方案分离的。为了评估这两组细胞的优势,本研究首次尝试在常氧和低氧培养条件下比较人 FAA-CP 和 MCP,研究它们的生长特性、表面标志物特征和三系潜能。通过检测软骨形成和肥大标志物(Aggrecan 和 COL2A1/COL1A1 比值)的 mRNA 表达、糖胺聚糖含量(GAG)和组织学染色来评估它们的软骨形成潜力。MCP 表现出较低水平的肥大标志物(RUNX2 和 COL1A1),常氧-MCP 表现出显著更高水平的软骨形成标志物(Aggrecan 和 COL2A1/COL1A1 比值),因此具有更好的软骨修复潜力。在软骨诱导后,常氧-MCP 也显示出更高水平的 GAG/DNA,染色更强。需要对 MCP 进行更深入的研究,因为它们可能是生成类似透明软骨的修复组织的合适候选物。