Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
Mol Med Rep. 2012 Nov;6(5):1183-9. doi: 10.3892/mmr.2012.1039. Epub 2012 Aug 17.
Improved knowledge of the immunological properties of mesenchymal stem cells (MSCs) creates a potential cell-mediated immunotherapeutic approach for arthritic diseases. The low frequency of MSCs necessitates their in vitro expansion prior to clinical use. As sequential passage has been used as the most popular strategy for expansion of MSCs, the effect of long-term culture on the immunological properties of MSCs is not clear. In this study, we observed that the morphology of MSCs showed the typical characteristics of the Hayflick model of cellular aging during sequential expansion. The growth kinetics of MSCs decreased while the number of MSCs staining positive for SA β-gal (senescence marker) increased in long-term culture. Although long-term culture exerts less of an effect on the immunophenotype of MSCs, the immunosuppressive effects of MSCs on the allogeneic T-cell proliferation, activation-antigen expression (CD69 and CD25) and cytokine production (IFN-γ, TNF-α, IL-10) were significantly impaired following stimulation with phytohemagglutinin (PHA).
对间充质干细胞（MSCs）免疫特性的深入了解为关节炎疾病的细胞介导免疫治疗方法创造了潜力。由于 MSCs 的频率较低，因此在临床使用前需要进行体外扩增。由于传代培养已被用作 MSC 扩增的最常用策略，因此长期培养对 MSCs 免疫特性的影响尚不清楚。在这项研究中，我们观察到 MSCs 在连续扩增过程中表现出典型的细胞衰老 Hayflick 模型特征。在长期培养中，MSC 的生长动力学下降，而 SAβ-gal（衰老标志物）染色阳性的 MSC 数量增加。尽管长期培养对 MSCs 的免疫表型影响较小，但在植物血凝素（PHA）刺激下，MSC 对同种异体 T 细胞增殖、活化抗原表达（CD69 和 CD25）和细胞因子产生（IFN-γ、TNF-α、IL-10）的抑制作用明显受损。
