The presence of mesenchymal progenitor cells (MPCs) in rheumatoid arthritis (RA) articular cartilage is sparsely investigated largely owing to the persistent pathogenic disease condition and lack of specific biomarkers. Considering the recent advancements for potential cell-based therapies in immunomodulatory diseases, such as RA, this in vitro study was aimed at investigating the cellular, molecular and differentiation characteristics of human RA cartilage-derived MPCs. Articular cartilage fragments from RA patients were obtained for the isolation and characterization of MPCs on their cellular and biological properties, cytogenic stability, pluripotency, and plasticity. Established MPCs were phenotypically identified using a panel of markers and their differentiation ability into mesenchymal lineages was assessed by cytochemical staining and the expression of molecular markers. MPCs displayed a heterogeneous population of cells with characteristic features of multipotent stem cells. Cells had higher viability, proliferative rate and colony-forming ability. Further, MPCs showed the expression of pluripotency markers, cytogenetic stability and minimal replicative senescence. In addition, MPCs differentiated into osteocytes, adipocytes and chondrocytes, and modulated the expression of each lineage-specific gene markers. The results demonstrated the availability of a viable pool of MPCs residing in RA cartilage, which could serve as an ideal cell source for reinstating native homotypic cartilage.


中文翻译：

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人类风湿性关节炎软骨间充质祖细胞的分子特征和分化

类风湿性关节炎（RA）关节软骨中间充质祖细胞（MPC）的存在很少被研究，这主要是由于持续的致病性疾病状况和缺乏特异性生物标志物。考虑到免疫调节疾病（例如 RA）潜在细胞疗法的最新进展，这项体外研究旨在研究人类 RA 软骨来源的 MPC 的细胞、分子和分化特征。获得 RA 患者的关节软骨碎片，用于分离 MPC 并对其细胞和生物学特性、细胞稳定性、多能性和可塑性进行表征。使用一组标记对建立的 MPC 进行表型鉴定，并通过细胞化学染色和分子标记的表达评估它们分化为间充质谱系的能力。MPCs 显示出具有多能干细胞特征的异质细胞群。细胞具有较高的活力、增殖率和集落形成能力。此外，MPC 还表现出多能性标记的表达、细胞遗传学稳定性和最小的复制衰老。此外，MPC 分化为骨细胞、脂肪细胞和软骨细胞，并调节每种谱系特异性基因标记的表达。结果证明了 RA 软骨中存在可行的 MPC 池，这可以作为恢复天然同型软骨的理想细胞来源。