Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells
Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells
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DOI：
10.3389/fphar.2020.01004
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发表时间：
2020-07
影响因子：
5.6
通讯作者：
Shuang Liu;T. Kiyoi;Marina Ishida;M. Mogi
中科院分区：
文献类型：
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作者：
Shuang Liu;T. Kiyoi;Marina Ishida;M. Mogi
基于间充质干细胞（MSC）的关节再生可能有利于在类风湿性关节炎的治疗中保护和重建软骨组织。然而，目前尚不清楚当前的免疫抑制策略如何影响间充质干细胞的多能性。本研究旨在分析主要抗风湿药物（包括甲氨蝶呤、泼尼松龙、阿达木单抗和托珠单抗）对 MSC 多能性的直接有效性，特别关注软骨形成。在体外分化系统中观察到甲氨蝶呤对脂肪生成、骨生成和软骨生成的抑制作用以剂量依赖性方式发生。泼尼松龙增强脂肪生成，但降低骨祖细胞中的碱性磷酸酶活性并抑制软骨球的形成。阿达木单抗抑制碱性磷酸酶活性，而托珠单抗在体外减少 MSC 的成骨和软骨形成。还使用支架球体移植小鼠模型在体内评估了抗风湿药物处理的 MSC 的软骨形成。所检查的生物制剂似乎对于软骨形成相对安全，但甲氨蝶呤和泼尼松龙对软骨形成表现出相反的影响。总而言之，这些结果揭示了主要抗风湿药物对 MSC 多能性的直接功效。因此，我们的研究结果表明，涉及软骨组织工程的治疗方法需要进一步优化药物方案。
Mesenchymal stem cell (MSC)–based articular regeneration might be beneficial for both protecting and rebuilding cartilaginous tissues in the management of rheumatoid arthritis. However, it is unclear how current immunosuppressive strategies influence the multipotency of MSCs. The present study was undertaken to profile the direct effectiveness of major antirheumatic drugs including methotrexate, prednisolone, adalimumab, and tocilizumab on the multipotency of MSCs, with a special focus on chondrogenesis. The inhibitory effects of methotrexate on adipogenesis, osteogenesis, and chondrogenesis were observed to occur in a dose-dependent manner in an in vitro differentiation system. Prednisolone enhanced adipogenesis, but reduced alkaline phosphatase activity in osteoprogenitors and suppressed the formation of chondrospheroids. Adalimumab suppressed alkaline phosphatase activity, while tocilizumab diminished osteogenesis and chondrogenesis of MSCs in vitro. Chondrogenesis of antirheumatic drug-treated MSCs was also evaluated in vivo using a scaffolded spheroid-engrafted murine model. The biologics examined appeared to be relatively safe for cartilaginous formation, but methotrexate and prednisolone exhibited opposing influences on chondrogenesis. Taken together, these results reveal the direct efficacy of major antirheumatic agents on the multipotency of MSCs. Therefore, our findings suggest that optimization of medication protocols is further required for therapeutic approaches involving cartilaginous tissue engineering.