A three-dimensional model of human lung development and disease from pluripotent stem cells.
A three-dimensional model of human lung development and disease from pluripotent stem cells.
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人类肺发育和疾病的三维模型来自多能干细胞。
DOI：
10.1038/ncb3510
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发表时间：
2017-05
影响因子：
21.3
通讯作者：
Snoeck HW
中科院分区：
文献类型：
--
作者：
Chen YW;Huang SX;de Carvalho ALRT;Ho SH;Islam MN;Volpi S;Notarangelo LD;Ciancanelli M;Casanova JL;Bhattacharya J;Liang AF;Palermo LM;Porotto M;Moscona A;Snoeck HW
在三维（3D）环境下从人多能干细胞（hPSCs）重现肺发育过程，将使人们更深入地了解人类发育，以及为疾病建模、药物研发和再生医学制定创新策略。在此我们报道从hPSCs生成肺芽类器官（LBOs），其包含中胚层和肺内胚层，并且在异种移植后以及在基质胶3D培养中发育成分支气道和早期肺泡结构。表达分析和结构特征表明，这些分支结构达到了人类妊娠中期的水平。用呼吸道合胞病毒在体外感染（该病毒会导致婴儿小气道阻塞和细支气管炎），会使受感染的细胞肿胀、脱落并掉入类器官腔中，这与人肺中的观察结果相似。引入HPS1突变（该突变会导致一种早发型难治性肺纤维化），会导致细胞外基质和间充质细胞的积聚，这表明该模型有可能用于在体外重现纤维化肺病。因此，LBOs重现了肺发育过程，并可能为肺部疾病建模提供一种有用的工具。
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modeling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease.
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影响因子：
16.6
作者：
Jain, Rajan;Barkauskas, Christina E.;Takeda, Norifumi;Bowie, Emily J.;Aghajanian, Haig;Wang, Qiaohong;Padmanabhan, Arun;Manderfield, Lauren J.;Gupta, Mudit;Li, Deqiang;Li, Li;Trivedi, Chinmay M.;Hogan, Brigid L. M.;Epstein, Jonathan A.
通讯作者：
Epstein, Jonathan A.
影响因子：
9.2
作者：
Pepicelli, CV;Lewis, PM;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
16.6
作者：
Alanis, Denise Martinez;Chang, Daniel R.;Akiyama, Haruhiko;Krasnow, Mark A.;Chen, Jichao
通讯作者：
Chen, Jichao
影响因子：
1.5
作者：
Perl, AKT;Kist, R;Whitsett, JA
通讯作者：
Whitsett, JA
DOI：
10.1165/rcmb.2012-0347oc
发表时间：
2013-06-01
影响因子：
6.4
作者：
Liu, Li;Kugler, Matthias C.;Munger, John S.
通讯作者：
Munger, John S.