An in Vitro and in Vivo Study of the Effect of Dexamethasone on Immunoinhibitory Function of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells.
An in Vitro and in Vivo Study of the Effect of Dexamethasone on Immunoinhibitory Function of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells.
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地塞米松对诱导多能干细胞来源的间充质干细胞免疫抑制功能影响的体外和体内研究。
DOI：
10.1177/0963689718780194
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发表时间：
2018-09
影响因子：
3.3
通讯作者：
Fu QL
中科院分区：
文献类型：
--
作者：
Wang D;Sun YQ;Gao WX;Fan XL;Shi JB;Fu QL
诱导多能干细胞衍生的间充质干细胞（iPSC-MSC）代表了用于患者特异性细胞治疗的有前途的细胞来源。我们以前证明，他们显示对过敏性气道炎症的免疫调节作用。糖皮质激素是一种强有力的抗炎化合物，广泛应用于过敏性疾病的治疗。然而，糖皮质激素对iPSC-MSCs的免疫调节功能的影响仍然未知。本研究旨在探讨地塞米松（Dex）对iPSC-MSCs免疫调节功能的影响。从骨髓细胞衍生的iPSC产生总共三个人iPSC-MSC克隆。采用CD 3/CD 28抗体诱导的外周血单个核细胞（PBMC）增殖实验，观察Dex对iPSC-MSCs免疫抑制功能的影响。诱导接触性超敏反应（CHS）和过敏性气道炎症的小鼠模型，并且用iPSC-MSC和Dex单独和组合的治疗来分析小鼠中的炎症水平。结果表明，Dex不干扰iPSC-MSCs对PBMC增殖的免疫抑制作用。在CHS小鼠中，同时用Dex治疗不影响iPSC-MSC对区域引流淋巴结和发炎的耳组织中的炎症的作用。此外，iPSC-MSCs与Dex的联合给药降低了CHS小鼠耳中干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的局部表达。在过敏性气道炎症的小鼠模型中，iPSC-MSC治疗与Dex组合导致与单独iPSC-MSC或Dex治疗相似程度的肺部炎症减轻。总之，Dex在体外和体内均不显著影响iPSC-MSCs的免疫调节功能。当iPSC-MSC和糖皮质激素共同施用时，这些发现可能具有影响。
Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) represent a promising cell source for patient-specific cell therapy. We previously demonstrated that they display an immunomodulatory effect on allergic airway inflammation. Glucocorticoids are powerful anti-inflammatory compounds and widely used in the therapy of allergic diseases. However, the effect of glucocorticoids on the immunomodulatory function of iPSC-MSCs remains unknown. This study aimed to determine the effect of dexamethasone (Dex) on the immunomodulatory function of iPSC-MSCs in vitro and in vivo. A total of three human iPSC-MSC clones were generated from amniocyte-derived iPSCs. Anti-CD3/CD28-induced peripheral blood mononuclear cell (PBMC) proliferation was used to assess the effect of Dex on the immunoinhibitory function of iPSC-MSCs in vitro. Mouse models of contact hypersensitivity (CHS) and allergic airway inflammation were induced, and the levels of inflammation in mice were analyzed with the treatments of iPSC-MSCs and Dex, alone and combined. The results showed that Dex did not interfere with the immunoinhibitory effect of iPSC-MSCs on PBMC proliferation. In CHS mice, simultaneous treatment with Dex did not affect the effect of iPSC-MSCs on the inflammation, both in regional draining lymph nodes and in inflamed ear tissue. In addition, co-administration of iPSC-MSCs with Dex decreased the local expression of interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the ears of CHS mice. In the mouse model of allergic airway inflammation, iPSC-MSC treatment combined with Dex resulted in a similar extent of reduction in pulmonary inflammation as iPSC-MSCs or Dex treatment alone. In conclusion, Dex does not significantly affect the immunomodulatory function of iPSC-MSCs both in vitro and in vivo. These findings may have implications when iPSC-MSCs and glucocorticoids are co-administered.
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影响因子：
4
作者：
Kimbrel, Erin A.;Kouris, Nicholas A.;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
6
作者：
Chen, Yen Shun;Pelekanos, Rebecca A.;Fisk, Nicholas M.
通讯作者：
Fisk, Nicholas M.
源自人类诱导多能干细胞的间充质干细胞调节过敏性鼻炎的 T 细胞表型
影响因子：
12.4
作者：
Fu, Q. L.;Chow, Y. Y.;Xu, G.
通讯作者：
Xu, G.
DOI：
10.2215/cjn.04950610
发表时间：
2011-02-01
影响因子：
9.8
作者：
Perico, Norberto;Casiraghi, Federica;Remuzzi, Giuseppe
通讯作者：
Remuzzi, Giuseppe
影响因子：
--
作者：
Pan GH;Chen Z;Xu L;Zhu JH;Xiang P;Ma JJ;Peng YW;Li GH;Chen XY;Fang JL;Guo YH;Zhang L;Liu LS
通讯作者：
Liu LS