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骨髓间充质干细胞经气管内移植可减轻哮喘小鼠气道炎症并上调 CD4⁺CD25⁺调节性 T 细胞。

Intratracheal transplantation of bone marrow-derived mesenchymal stem cells reduced airway inflammation and up-regulated CD4⁺CD25⁺ regulatory T cells in asthmatic mouse.

机构信息

Department of Respiratory Medicine, Changhai Hospital of Second Military Medical University, Shanghai 200433, China.

出版信息

Cell Biol Int. 2013 Jul;37(7):675-86. doi: 10.1002/cbin.10084. Epub 2013 Apr 4.

Abstract

Mesenchymal stem cells attenuate the severity of lung injury due to their immunomodulatory properties. The effect of bone marrow-derived mesenchymal stem cells on asthma is seldom reported. We have examined the effect of BMSCs on airway inflammation in asthma. Forty female BALB/c mice were equally randomised into PBS group, BMSCs treatment group, BMSCs control group and asthmatic group. Reactivity of the airway to acetylcholine was measured by barometric plethysmography. Cytokine profiles of bronchoalveolar lavage fluid and serum were determined by enzyme-linked immunosorbent assay. Morphometric analysis was done with haematoxylin and periodic-acid Schiff staining. Engraftment of BMSCs in asthmatic mice significantly decreased the number of eosinophils and mononuclear cells in bronchoalveolar lavage fluid and the airway (P < 0.05). Both goblet cell hyperplasia and responsiveness to acetylcholine were significantly reduced in BMSCs treatment groups. Moreover, BMSCs engraftment caused significant increases the ratio of Treg in pulmonary lymph node and interleukin-10 (IL-10) and interleukin-12 levels in BALF and serum. We conclude that BMSCs engraftment ameliorated airway inflammation and improved lung function in asthmatic mouse and the protective effect might be mediated by upregulating Treg and partly involved with increasing IL-10.

摘要

间充质干细胞通过其免疫调节特性减轻肺损伤的严重程度。骨髓来源的间充质干细胞对哮喘的作用很少有报道。我们研究了骨髓间充质干细胞对哮喘气道炎症的影响。将 40 只雌性 BALB/c 小鼠等分为 PBS 组、BMSCs 治疗组、BMSCs 对照组和哮喘组。通过气压测流仪测量气道对乙酰胆碱的反应性。通过酶联免疫吸附试验测定支气管肺泡灌洗液和血清中的细胞因子谱。用苏木精和过碘酸希夫染色进行形态计量分析。骨髓间充质干细胞在哮喘小鼠中的植入显著减少了支气管肺泡灌洗液和气道中的嗜酸性粒细胞和单核细胞数量(P<0.05)。BMSCs 治疗组的杯状细胞增生和对乙酰胆碱的反应性均显著降低。此外,骨髓间充质干细胞的植入导致肺淋巴结中 Treg 比例以及 BALF 和血清中白细胞介素-10(IL-10)和白细胞介素-12 水平显著增加。我们的结论是,骨髓间充质干细胞的植入改善了哮喘小鼠的气道炎症和肺功能,其保护作用可能是通过上调 Treg 部分介导的,部分涉及增加 IL-10。

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