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TNF-α 抑制剂通过增强免疫抑制作用逆转人脐带间充质干细胞对实验性关节炎的作用。

TNF-α inhibitor reverse the effects of human umbilical cord-derived stem cells on experimental arthritis by increasing immunosuppression.

机构信息

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.

出版信息

Cell Immunol. 2012;273(1):30-40. doi: 10.1016/j.cellimm.2011.11.009. Epub 2011 Dec 8.

Abstract

To demonstrate the therapeutic potential for cartilage repair of mesenchymal stem cells derived from human umbilical cord (HUCSC), we studied the clinical and histopathological effects of intra-articular injection of HUCSCs in a collagen-induced arthritis (CIA) model. In our study, intra-articular injection of HUCSCs had no benefit in CIA mice; and accelerated the progression of arthritis in the presence of TNF-α. To determine the role of TNF-α, we injected the combination with HUCSCs and TNF inhibitor, showed reduced the disease signs in CIA mice. On exposure of TNF-α, stem cells significantly decreased the expression of CD90, HLA-G, and the levels of IL-10 in vitro and in vivo. Our data showed that TNF-α blocks the immunosuppressive effects of HUCSCs and that inhibition of TNF-α decreases cartilage destruction by suppressing the immunogenicity of HUCSCs. Injecting both a TNF inhibitor and HUCSCs may be a potential effective therapy for ameliorating the disease.

摘要

为了展示源自人脐带间充质干细胞(HUCSC)的软骨修复治疗潜力,我们研究了关节内注射 HUCSC 对胶原诱导关节炎(CIA)模型的临床和组织病理学影响。在我们的研究中,关节内注射 HUCSC 对 CIA 小鼠没有益处;并且在 TNF-α 存在的情况下加速了关节炎的进展。为了确定 TNF-α 的作用,我们将 HUCSC 与 TNF 抑制剂联合注射,结果显示 CIA 小鼠的疾病症状减轻。在 TNF-α 的作用下,干细胞在体外和体内均显著降低了 CD90、HLA-G 的表达和 IL-10 的水平。我们的数据表明,TNF-α 阻断了 HUCSC 的免疫抑制作用,而抑制 TNF-α 通过抑制 HUCSC 的免疫原性来减少软骨破坏。同时注射 TNF 抑制剂和 HUCSC 可能是改善疾病的一种潜在有效治疗方法。

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