Huang Sarah X L, Islam Mohammad Naimul, O'Neill John, Hu Zheng, Yang Yong-Guang, Chen Ya-Wen, Mumau Melanie, Green Michael D, Vunjak-Novakovic Gordana, Bhattacharya Jahar, Snoeck Hans-Willem
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA. [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Nat Biotechnol. 2014 Jan;32(1):84-91. doi: 10.1038/nbt.2754. Epub 2013 Dec 1.
The ability to generate lung and airway epithelial cells from human pluripotent stem cells (hPSCs) would have applications in regenerative medicine, modeling of lung disease, drug screening and studies of human lung development. We have established, based on developmental paradigms, a highly efficient method for directed differentiation of hPSCs into lung and airway epithelial cells. Long-term differentiation of hPSCs in vivo and in vitro yielded basal, goblet, Clara, ciliated, type I and type II alveolar epithelial cells. The type II alveolar epithelial cells were capable of surfactant protein-B uptake and stimulated surfactant release, providing evidence of specific function. Inhibiting or removing retinoic acid, Wnt and BMP-agonists to signaling pathways critical for early lung development in the mouse-recapitulated defects in corresponding genetic mouse knockouts. As this protocol generates most cell types of the respiratory system, it may be useful for deriving patient-specific therapeutic cells.
从人多能干细胞（hPSC）生成肺和气道上皮细胞的能力在再生医学、肺病建模、药物筛选以及人类肺发育研究中具有应用价值。基于发育范式，我们建立了一种将hPSC定向分化为肺和气道上皮细胞的高效方法。hPSC在体内和体外的长期分化产生了基底细胞、杯状细胞、克拉拉细胞、纤毛细胞、I型和II型肺泡上皮细胞。II型肺泡上皮细胞能够摄取表面活性蛋白B并刺激表面活性物质释放，提供了特定功能的证据。抑制或去除对小鼠早期肺发育至关重要的信号通路中的视黄酸、Wnt和BMP激动剂，重现了相应基因敲除小鼠中的缺陷。由于该方案可生成呼吸系统的大多数细胞类型，因此可能有助于获得患者特异性治疗细胞。
