Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.
Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.
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DOI：
10.1089/scd.2014.0512
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发表时间：
2015-07-15
影响因子：
4
通讯作者：
Vallier L
中科院分区：
文献类型：
--
作者：
Hannan NR;Sampaziotis F;Segeritz CP;Hanley NA;Vallier L
总体而言，肺部疾病是全球过早死亡的最大原因之一，也是再生医学领域的一个主要焦点。尽管取得了重大进展，但目前只有少数干细胞平台可用于肺部疾病的基于细胞的治疗、疾病建模和药物筛选。人类前肠干细胞(HFSCs)代表了一种有利的祖细胞类型，可用于扩增大量细胞用于再生医学，并可从任何人类多能干细胞系中分离出来。在这里，我们通过产生一个几乎均一的早期肺内皮细胞群来进一步展示hFSCs的应用，该群体共表达Nkx2.1和FOXP2。然后，这些祖细胞能够形成以远端呼吸道上皮为代表的细胞，表达Nkx2.1、GATA6和囊性纤维化跨膜传导调节因子(CFTR)并分泌SFTPC。该培养体系可应用于携带cftr突变ΔF508的人胚胎干细胞，使囊性纤维化体外模型的建立成为可能。该平台与药物筛选和小分子功能验证兼容，可以逆转CFTR突变相关的表型。这是首次证明多能内胚层干细胞不仅可以分化为肝脏和胰腺细胞，还可以分化为肺内胚层。此外，我们的研究建立了一种新的方法来产生功能肺细胞，可以用于疾病建模以及药物筛选和肺发育研究。
Collectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an advantageous progenitor cell type that can be used to amplify large quantities of cells for regenerative medicine applications and can be derived from any human pluripotent stem cell line. Here, we further demonstrate the application of hFSCs by generating a near homogeneous population of early pulmonary endoderm cells coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that are representative of distal airway epithelium that express NKX2.1, GATA6, and cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC. This culture system can be applied to hFSCs carrying the CFTR mutation Δf508, enabling the development of an in vitro model for cystic fibrosis. This platform is compatible with drug screening and functional validations of small molecules, which can reverse the phenotype associated with CFTR mutation. This is the first demonstration that multipotent endoderm stem cells can differentiate not only into both liver and pancreatic cells but also into lung endoderm. Furthermore, our study establishes a new approach for the generation of functional lung cells that can be used for disease modeling as well as for drug screening and the study of lung development.
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DOI：
10.1513/pats.200801-006aw
发表时间：
2008-08-15
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Rawlins, Emma L
通讯作者：
Rawlins, Emma L
影响因子：
23.9
作者：
Seki, Tomohisa;Yuasa, Shinsuke;Fukuda, Keiichi
通讯作者：
Fukuda, Keiichi
影响因子：
11.4
作者：
PETERS, K;WERNER, S;WILLIAMS, L
通讯作者：
WILLIAMS, L
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
24.3
作者：
Forrest, IA;Murphy, DM;Corris, PA
通讯作者：
Corris, PA