气管内给予脂肪间充质干细胞可缓解小鼠慢性哮喘模型。
Intratracheal administration of adipose derived mesenchymal stem cells alleviates chronic asthma in a mouse model.
机构信息
Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, NO.197, Ruijin Er Road, Shanghai, 200025, China.
School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
出版信息
BMC Pulm Med. 2018 Aug 8;18(1):131. doi: 10.1186/s12890-018-0701-x.
BACKGROUND
Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model.
METHODS
Murine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR.
RESULTS
The mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1β (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ.
CONCLUSIONS
Intratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs.
背景
脂肪间充质干细胞（ASCs）在哮喘中发挥免疫调节作用。然而，其潜在机制尚不清楚。本研究旨在通过卵清蛋白（OVA）致敏的哮喘小鼠模型探讨 ASCs 对慢性哮喘的影响和机制。
方法
从雄性 Balb/c 小鼠中分离出小鼠 ASCs（mASCs），并通过流式细胞术检测表面标志物的表达进行鉴定。建立 OVA 致敏的哮喘小鼠模型，然后通过气管内给药给予 mASCs 治疗。通过测量气道反应性、进行免疫组织化学分析和检查支气管肺泡灌洗液（BALF）来评估治疗效果。此外，通过 CHIP 和 ELISA 分别检测炎症细胞因子和 lgE 的表达。使用 qRT-PCR 检测血清指标的 mRNA 水平。
结果
mASCs 通过贴壁生长，呈成纤维细胞样形态，并且表现出 CD90、CD44 和 CD29 的阳性表达以及 CD45 和 CD34 的阴性表达，表明 mASCs 已成功分离。通过气管内给药将 mASCs 给予哮喘模型动物可降低气道反应性、淋巴细胞数量（P<0.01）和 lgE 的表达（P<0.01）、IL-1β（P<0.05）、IL-4（P<0.001）和 IL-17F（P<0.001），增加血清中 IL-10 和 Foxp3 的水平以及脾中 CD4+CD25+Foxp3+Tregs 的比例，并降低 IL-17（P<0.05）和 RORγ的表达。
结论
气管内给予 mASCs 可减轻 OVA 致敏哮喘模型中的气道炎症、改善气道重塑和缓解气道高反应性，这可能与 mASCs 恢复 Th1/Th2 细胞平衡有关。
Zotero 插件