Osthole enhances the immunosuppressive effects of bone marrow-derived mesenchymal stem cells by promoting the Fas/FasL system.

Osthole enhances the immunosuppressive effects of bone marrow-derived mesenchymal stem cells by promoting the Fas/FasL system.
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蛇床子素通过促进Fas/FasL系统增强骨髓间充质干细胞的免疫抑制作用

DOI:
10.1111/jcmm.16459
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发表时间:
2021-05
影响因子:
5.3
通讯作者:
Yang D
Yang D
中科院分区:
医学2区
文献类型:
--
作者:
Yu Y;Chen M;Yang S;Shao B;Chen L;Dou L;Gao J;Yang D

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由于易于收获和逃避免疫排斥的优点,自体骨髓源性间充质干细胞(BMSCs)是针对炎症和自身免疫性疾病的免疫抑制治疗的有希望的候选者。然而,由于BMSCs的免疫调节特性总是受到患者免疫发病机制的损害,因此该治疗仍然具有挑战性。蛇床子素因其可靠而广泛的生物活性而受到越来越多的临床关注。在这项研究中,我们发现来源于骨质疏松症供体的BMSCs在实验性炎症性结肠炎和骨质疏松症的细胞治疗中无效。体内和体外实验表明,由于Fas和FasL表达下调,骨髓间充质干细胞诱导T细胞凋亡的能力下降。通过应用蛇床子素,我们成功地恢复了骨髓间充质干细胞的免疫抑制能力,提高了其对实验性炎症性结肠炎和骨质疏松症的治疗效果。此外,我们发现蛇床子素预处理后BMSCs的免疫调节特性增强。在这项研究中,我们的数据突出了一种新的药理学修饰方法(即蛇床子素),以改善来自健康或炎症微环境的BMSC的免疫调节性能。这些发现可能会显着改善靶向策略的发展,以加强免疫抑制治疗BMSCs。
Thanks to the advantages of easy harvesting and escape from immune rejection, autologous bone marrow‐derived mesenchymal stem cells (BMSCs) are promising candidates for immunosuppressive therapy against inflammation and autoimmune diseases. However, the therapy is still challenging because the immunomodulatory properties of BMSCs are always impaired by immunopathogenesis in patients. Because of its reliable and extensive biological activities, osthole has received increased clinical attention. In this study, we found that BMSCs derived from osteoporosis donors were ineffective in cell therapy for experimental inflammatory colitis and osteoporosis. In vivo and in vitro tests showed that because of the down‐regulation of Fas and FasL expression, the ability of osteoporotic BMSCs to induce T‐cell apoptosis decreased. Through the application of osthole, we successfully restored the immunosuppressive ability of osteoporotic BMSCs and improved their treatment efficacy in experimental inflammatory colitis and osteoporosis. In addition, we found the immunomodulatory properties of BMSCs were enhanced after osthole pre‐treatment. In this study, our data highlight a new approach of pharmacological modification (ie osthole) to improve the immune regulatory performance of BMSCs from a healthy or inflammatory microenvironment. The development of targeted strategies to enhance immunosuppressive therapy using BMSCs may be significantly improved by these findings.
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