Distal airway stem cells ameliorate bleomycin-induced pulmonary fibrosis in mice
Distal airway stem cells ameliorate bleomycin-induced pulmonary fibrosis in mice
复制标题
远端气道干细胞改善博莱霉素诱导的小鼠肺纤维化
DOI：
10.1186/s13287-019-1257-2
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发表时间：
2019-06-03
影响因子：
7.5
通讯作者：
Jin, Faguang
中科院分区：
文献类型：
--
作者：
Shi, Yun;Dong, Mingqing;Jin, Faguang
背景特发性肺纤维化是以肺上皮细胞丢失和纤维化进程不可避免为特征的疾病，目前尚无有效的治疗方法。远端气道干/祖细胞（DASC）已被证明在肺损伤后具有强大的再生能力。在这项工作中，我们的目的是定义的作用，小鼠DASC（mDASC）在博莱霉素诱导的小鼠肺fibrosis.MethodsThe的mDASC分离，在体外扩增，并标记GFP慢病毒感染。在第7天将标记的mDASC经气管内滴注到博来霉素诱导的肺纤维化小鼠中。分别于用药后7、14、21 d观察肺组织病理学改变、胶原含量、α-SMA表达、肺功能及死亡率。结果移植的mDASCs在博莱霉素损伤的肺组织中可整合、增殖并分化为I型肺泡上皮细胞。它们还通过减少胶原沉积和α-SMA的表达来抑制纤维形成。此外，mDASC改善肺功能，降低博莱霉素诱导的肺纤维化mice.ConclusionsThe数据强烈表明，mDASC可以改善博莱霉素诱导的肺纤维化，促进肺再生和抑制肺纤维化。
BackgroundIdiopathic pulmonary fibrosis is characterized by loss of lung epithelial cells and inexorable progression of fibrosis with no effective and approved treatments. The distal airway stem/progenitor cells (DASCs) have been shown to have potent regenerative capacity after lung injury. In this work, we aimed to define the role of mouse DASCs (mDASCs) in response to bleomycin-induced lung fibrosis in mice.MethodsThe mDASCs were isolated, expanded in vitro, and labeled with GFP by lentiviral infection. The labeled mDASCs were intratracheally instilled into bleomycin-induced pulmonary fibrosis mice on day 7. Pathological change, collagen content, α-SMA expression, lung function, and mortality rate were assessed at 7, 14, and 21 days after bleomycin administration. Tissue section and direct fluorescence staining was used to show the distribution and differentiation of mDASCs in lung.ResultsThe transplanted mDASCs could incorporate, proliferate, and differentiate into type I pneumocytes in bleomycin-injured lung. They also inhibited fibrogenesis by attenuating the deposition of collagen and expression of α-SMA. In addition, mDASCs improved pulmonary function and reduce mortality in bleomycin-induced pulmonary fibrosis mice.ConclusionsThe data strongly suggest that mDASCs could ameliorate bleomycin-induced pulmonary fibrosis by promotion of lung regeneration and inhibition of lung fibrogenesis.