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与哮喘相关的基因,用人类胚胎干细胞衍生的间充质干细胞进行治疗。

The genes involved in asthma with the treatment of human embryonic stem cell-derived mesenchymal stem cells.

机构信息

Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Centre for Stem Cell Clinical Research and Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

出版信息

Mol Immunol. 2018 Mar;95:47-55. doi: 10.1016/j.molimm.2018.01.013. Epub 2018 Feb 20.

DOI:10.1016/j.molimm.2018.01.013
PMID:29407576
Abstract

BACKGROUND

Asthma is affecting more than 300 million people worldwide, which represents the most common chronic disease among children. We previously found that mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) modulated the immune response on Th2-mediated asthma in vivo and in vitro. This study further evaluated the immunomodulatory effects of MSCs from human embryonic stem cells (hESCs) on asthma.

METHODS

Multipotent hESC-MSCs were obtained using a feeder-free method. The hESC-MSCs were analysed for the expression of stem cell surface markers by flow cytometry, their differentiation potentials were analysed using in vitro trilineage differentiation methods hESC-MSCs were transplanted into the murine model with ovalbumin (OVA)-induced airway allergic inflammation. The expression levels of allergic related genes were measured by the mRNA PCR arrays.

RESULTS

The hESC-MSCs expressed classical MSC markers and held the capability of differentiation into multiple mesoderm-type cell lineages. hESC-MSCs were able to suppress allergic inflammation by modulating Th2 cells and eosinophils in the mice, and reversed the reduction of regulatory T cells. By using PCR array, 5 mRNAs- chemokine (C-C motif) ligand 11 (Ccl11), Ccl24, interleukin13 (Il13), Il33 and eosinophil-associated, ribonuclease A family, member 11 (Ear11) were identified the most relevant in murine airway allergic inflammation and hESC-MSCs treatment.

CONCLUSIONS

The therapeutic effects of hESC-MSCs were identified in the murine model of airway allergic inflammation with key mRNAs involved. This study will provide a better understanding regarding the mechanisms underlying hESC-MSCs therapeutic application in airway allergic inflammation.

摘要

背景

哮喘影响着全球超过 3 亿人,是儿童中最常见的慢性疾病。我们之前发现,诱导多能干细胞(iPSCs)衍生的间充质干细胞(MSCs)在体内和体外调节了 Th2 介导的哮喘的免疫反应。本研究进一步评估了人胚胎干细胞(hESCs)来源的 MSCs 对哮喘的免疫调节作用。

方法

使用无饲养层的方法获得多能 hESC-MSCs。通过流式细胞术分析 hESC-MSCs 表面干细胞标志物的表达,通过体外三系分化方法分析其分化潜能。将 hESC-MSCs 移植到卵清蛋白(OVA)诱导的气道过敏性炎症的小鼠模型中。通过 mRNA PCR 阵列测量过敏相关基因的表达水平。

结果

hESC-MSCs 表达经典的 MSC 标志物,并具有分化为多种中胚层细胞谱系的能力。hESC-MSCs 通过调节 Th2 细胞和小鼠中的嗜酸性粒细胞来抑制过敏性炎症,并逆转调节性 T 细胞的减少。通过使用 PCR 阵列,鉴定出 5 个 mRNA-趋化因子(C-C 基序)配体 11(Ccl11)、Ccl24、白细胞介素 13(Il13)、Il33 和嗜酸性粒细胞相关的、核糖核酸酶 A 家族、成员 11(Ear11)在小鼠气道过敏性炎症和 hESC-MSCs 治疗中最为相关。

结论

在气道过敏性炎症的小鼠模型中,鉴定出 hESC-MSCs 的治疗效果,涉及关键的 mRNAs。本研究将为 hESC-MSCs 治疗气道过敏性炎症的机制提供更好的理解。

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