All-Trans Retinoic Acid Improves the Effects of Bone Marrow-Derived Mesenchymal Stem Cells on the Treatment of Ankylosing Spondylitis: An In Vitro Study.

All-Trans Retinoic Acid Improves the Effects of Bone Marrow-Derived Mesenchymal Stem Cells on the Treatment of Ankylosing Spondylitis: An In Vitro Study.
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全反式视黄酸改善骨髓间充质干细胞治疗强直性脊柱炎的效果:体外研究

DOI:
10.1155/2015/484528
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发表时间:
2015
影响因子:
4.3
通讯作者:
Shen H
Shen H
中科院分区:
医学3区
文献类型:
--
作者:
Li D;Wang P;Li Y;Xie Z;Wang L;Su H;Deng W;Wu Y;Shen H

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先前的研究已经证明了全反式维甲酸(ATRA)和间充质干细胞(MSC)的免疫抑制作用。本研究旨在评估全反式维甲酸对骨髓间充质干细胞治疗强直性脊柱炎(AS)的免疫调节作用。用ATRA预处理健康供体的骨髓来源的MSC,并与来自AS患者的CD 3/28活化的外周血单个核细胞(PBMC)共培养。使用流式细胞术分析Th 17和调节性T(Treg)细胞的频率。采用流式细胞仪微球芯片和实时荧光定量PCR分别检测细胞因子的分泌和mRNA水平。ATRA预处理可增加MSCs分泌IL-6。ATRA预处理的MSC分别增加和减少了Th 17和Treg亚群。ATRA预处理的MSCs不仅能显著降低AS中重要的致病细胞因子肿瘤坏死因子-α(TNF-α),还能显著降低AS促进因子白细胞介素-17(IL-17 A)和干扰素-γ(IFN-γ)。这些结果表明,IL-6可能是AS的一个潜在的保护因素,并强调了ATRA在提高以MSC为基础的治疗AS的疗效方面的有希望的作用。
Previous studies have demonstrated the immunosuppressive effects of both all-trans retinoic acid (ATRA) and mesenchymal stem cells (MSCs). The present study aimed to assess the immunoregulatory effects of ATRA on MSCs in the treatment of ankylosing spondylitis (AS). Bone marrow-derived MSCs from healthy donors were pretreated with ATRA and cocultured with CD3/28-activated peripheral blood mononuclear cells (PBMCs) derived from AS patients. Frequencies of Th17 and regulatory T (Treg) cells were analyzed using flow cytometry. The secretion and the mRNA level of key cytokines were measured with cytometric bead array and quantitative real-time PCR, respectively. ATRA pretreatment increased interleukin-6 (IL-6) secretion of MSCs. Th17 and Treg subset populations were increased and reduced by ATRA-pretreated MSCs, respectively. ATRA-pretreated MSCs significantly decreased not only the vital pathogenic cytokine in AS, tumor necrosis factor-α (TNF-α), but also AS-boosting factors interleukin-17 (IL-17A) and interferon-γ (IFN-γ). These results indicated that IL-6 may be a potential protective factor in AS and highlighted the promising role of ATRA in improving the efficacy of MSC-based treatment of AS.
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