Dai Ranran, Liu Jia, Cai Songbai, Zheng Chengxiao, Zhou Xin
Department of Pulmonary Medicine, Shanghai General Hospital, Shanghai Jiaotong UniversityShanghai 200080, China.
Department of Pulmonary Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiaotong UniversityShanghai 200025, China.
Am J Transl Res. 2017 May 15;9(5):2421-2428. eCollection 2017.
Adipose-derived mesenchymal stem cells (ADMSCs) possess immunomodulation property, yet their therapeutic potential in asthma is unclear. This study aimed to explore the effects of ADMSCs on airway hyperresponsiveness and inflammation in ovalbumin (OVA)-induced asthma models. The underlying mechanism(s) was also examined. BALB/c mice were sensitized with OVA on days 0, 7, and 14, followed by 8-week OVA challenge from day 22. ADMSCs were injected via tail vein on day 21. Animals were measured for airway responsiveness, lung pathology, IgE and cytokine levels in serum, cell composition in bronchoalveolar lavage fluid (BALF), gene expression in the lung, and regulatory T cells (Tregs). We found that delivery of ADMSCs decreased airway responsiveness and eosinophil counts in BALF and reduced infiltration of inflammatory cells and number of mucus-expressing goblet cells in the lung in OVA-challenged mice. OVA-evoked elevation of serum IgE levels and alteration of cytokine production in serum and BALF was significantly prevented by ADMSCs. In addition, administration of ADMSCs impaired the regulation of lung IL-10, Foxp3, IL-17, and RORγ expression by OVA challenge and restored the percentage of CD4CD25Foxp3 Tregs in the spleen. In conclusion, ADMSCs confer protection against OVA-induced airway hyperresponsiveness and inflammation, which is associated with induction of Tregs and restoration of immune homeostasis. These findings suggest that ADMSCs may have therapeutic implications for allergic asthma.
脂肪来源的间充质干细胞(ADMSCs)具有免疫调节特性,但其在哮喘治疗中的潜力尚不清楚。本研究旨在探讨ADMSCs对卵清蛋白(OVA)诱导的哮喘模型中气道高反应性和炎症的影响。同时也研究了其潜在机制。在第0、7和14天用OVA对BALB/c小鼠进行致敏,从第22天开始进行为期8周的OVA激发。在第21天通过尾静脉注射ADMSCs。检测动物的气道反应性、肺病理学、血清中IgE和细胞因子水平、支气管肺泡灌洗液(BALF)中的细胞组成、肺中的基因表达以及调节性T细胞(Tregs)。我们发现,注射ADMSCs可降低OVA激发小鼠的气道反应性和BALF中的嗜酸性粒细胞计数,并减少肺中炎症细胞浸润和表达黏液的杯状细胞数量。ADMSCs显著抑制了OVA引起的血清IgE水平升高以及血清和BALF中细胞因子产生的改变。此外,ADMSCs给药削弱了OVA激发对肺IL-10、Foxp3、IL-17和RORγ表达的调节,并恢复了脾脏中CD4CD25Foxp3 Tregs的百分比。总之,ADMSCs可对OVA诱导的气道高反应性和炎症起到保护作用,这与Tregs的诱导和免疫稳态的恢复有关。这些发现表明ADMSCs可能对过敏性哮喘具有治疗意义。