类风湿关节炎中胚胎干细胞衍生间充质干细胞的免疫调节、抗滑膜细胞和抗破骨能力。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Eun-Yeong Bok , Won-Jae Lee , HyeonJeong Lee , Chan-Hee Jo , Chae-Yeon Hong , Seo-yoon Kang , Sanghyeon Park , Tae-Sung Hwang , Jaemin Kim , Sung-Lim Lee , Yong-Ho Choe , Sang-Il Lee
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引用次数: 0

摘要

类风湿性关节炎(RA)是一种慢性自身免疫性疾病,以关节炎症、成纤维细胞样滑膜细胞过度活化和破骨细胞介导的骨破坏为特征。来自成人组织的间充质干细胞(MSCs)由于其再生和免疫调节特性而显示出治疗潜力;然而,由于大规模生产和质量一致的限制,商业化仍然具有挑战性。相比之下,来自胚胎干细胞的间充质干细胞可以连续产生,并且表现出最小的变异,具有高度的生物学和遗传一致性。通过与脐带来源的MSCs (UC-MSCs)作为成人组织来源的MSCs的一种代表性类型进行比较,我们证实DW-MSCs具有MSC特征,包括增殖能力、表面标记物表达和体外免疫调节功能。我们通过体外FLS迁移和破骨细胞生成的实验进一步评估了它们对RA病理的影响。尽管DW-MSCs的免疫抑制能力低于UC-MSCs,但DW-MSCs保留了功能性免疫抑制效果,并表现出对FLS迁移和破骨细胞生成的优越抑制作用,这两者在RA的复杂发病机制中都是至关重要的。在胶原诱导的关节炎小鼠模型中,关节内注射DW-MSCs可减少炎症和骨侵蚀,并增加引流淋巴结的调节性T细胞/T-辅助-17比率。这些发现证明了DW-MSCs的治疗潜力,并支持其作为可扩展和标准化的干细胞治疗RA的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immunomodulatory, anti-synoviocyte, and anti-osteoclastic abilities of embryonic stem cell-derived mesenchymal stem cells in rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, fibroblast-like synoviocyte hyperactivation, and osteoclast-mediated bone destruction. Mesenchymal stem cells (MSCs) derived from adult tissues exhibit therapeutic potential owing to their regenerative and immunomodulatory properties; However, commercialization remains challenging due to limitations in large-scale production with consistent quality. Contrastingly, MSCs derived from embryonic stem cells can be continuously produced and exhibit minimal variation, with high biological and genetic uniformity. We confirmed that DW-MSCs exhibit MSC characteristics, including proliferative capacity, surface marker expression, and immunomodulatory function in vitro, by comparison with umbilical cord-derived MSCs (UC-MSCs) as one representative type of adult tissue-derived MSCs. We further evaluated their effects on RA pathology via in vitro assays of FLS migration and osteoclastogenesis. Although DW-MSCs showed lower immunosuppressive capacity than UC-MSCs, DW-MSCs retained functional immunosuppressive efficacy and exhibited superior inhibition of FLS migration and osteoclastogenesis, both of which are critical in the complex pathogenesis of RA. In a collagen-induced arthritis mouse model, intra-articular injection of DW-MSCs reduced inflammation and bone erosion, with an increased regulatory T cell/T-helper-17 ratio in draining lymph nodes. These findings demonstrated the therapeutic potential of DW-MSCs and support their application as a scalable and standardized stem cell-based treatment for RA.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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