Zhao Yiming, Lan Xu, Wang Yong, Xu Xiaoxi, Lu Shanzheng, Li Xiang, Zhang Baoren, Shi Ganggang, Gu Xiangying, Du Caigan, Wang Hao
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China.
Stem Cells Int. 2018 Jul 25;2018:3475137. doi: 10.1155/2018/3475137. eCollection 2018.
Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF- after ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1 and TNF-, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.
子宫内膜再生细胞（ERCs）最近被评估为一种有吸引力的新型干细胞疗法。先前的研究表明，大多数ERCs在注射后积聚在肺部，并成功用于治疗诸如心脏纤维化等疾病。然而，关于ERCs在特发性肺纤维化（IPF）中的相关研究尚未见报道。本研究旨在探讨ERCs对博莱霉素诱导的肺纤维化的影响。所有C57BL/6小鼠的IPF模型均通过气管内注射5mg/kg博莱霉素于PBS中诱导而成。从健康女性月经血中分离出ERCs，并在诱导后24小时静脉注射（100万/只小鼠）。在疾病诱导2周后评估湿/干重比测定、羟脯氨酸含量、病理和免疫组织学变化、丙二醛含量、总超氧化物歧化酶活性、细胞因子谱以及实时定量聚合酶链反应分析。结果表明，ERCs治疗显著降低了湿/干比并减少了胶原沉积。组织学分析、Masson染色和羟脯氨酸含量分析表明，ERCs可减少胶原纤维生成。免疫组织化学染色显示ERCs治疗后转化生长因子表达降低。此外，接受ERCs治疗的小鼠在肺和血清中白细胞介素-1和肿瘤坏死因子水平较低，但白细胞介素-10水平较高。基因表达分析表明，ERCs有力地抑制促凋亡基因Bax，同时增加抗凋亡基因Bcl-2以及抗纤维化基因HGF和基质金属蛋白酶-9。我们的结果表明，人ERCs通过免疫抑制和抗纤维化作用保护小鼠肺部免受肺纤维化影响。此外，这些发现为ERCs在临床治疗中的进一步应用奠定了基础。
