Journal Article

A three-dimensional model of human lung development and disease from pluripotent stem cells

Huang, Sarah Xuelian, Ciancanelli, Michael, de Carvalho, Ana Luisa Rodrigues Toste, Ho, Siu-Hong, Notarangelo, Luigi D., Bhattacharya, Jahar, Volpi, Stefano, Islam, Mohammad Naimul, Chen, Ya-Wen, Casanova, Jean-Laurent, Porotto, Matteo, Snoeck, Hans-Willem, Liang, Alice F., Moscona, Anne, Palermo, Laura M.

2017

Overview

Chen et al. generate lung bud organoids from human pluripotent stem cells that recapitulate early lung development, such as branching airway formation and early alveolar structures, which could potentially be used to model lung disease. 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 modelling, drug discovery and regenerative medicine 1 . 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 2 , led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs 3 . Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis 4 , 5 , 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Research
• Subject: 13/100 / 13/106 / 13/51 / 14/19 / 14/28 / 38/39 / 38/77 / 631/136 / 631/136/1425 / 631/136/2060 / 631/532/2064 / Age / Airway management / Airway obstruction / Alveoli / Animals / Bronchiolitis / Bronchopneumonia / Cancer Research / Cell Biology / Cell culture / Cell Culture Techniques / Cell cycle / Cell Differentiation / Cells / Cells, Cultured / Ciências Médicas / Cultured / Developmental Biology / Diseases / Drug discovery / Endoderm / Experiments / Extracellular matrix / Female / Genetic Predisposition to Disease / Health sciences / Human development / Humans / Immunology / Inbred NOD / letter / Life Sciences / Lumens / Lung / Lung - metabolism / Lung - pathology / Lung - virology / Lung diseases / Lung Transplantation / Male / Medicina Básica / Membrane Proteins / Membrane Proteins - genetics / Membrane Proteins - metabolism / Mesenchyme / Mesoderm / Mice / Mice, Inbred NOD / Mutation / Organogenesis / Organoids / Organoids - metabolism / Organoids - pathology / Organoids - transplantation / Organoids - virology / Phenotype / Pluripotency / Pluripotent Stem Cells / Pluripotent Stem Cells - metabolism / Pluripotent Stem Cells - pathology / Pluripotent Stem Cells - transplantation / Pluripotent Stem Cells - virology / Pulmonary Fibrosis / Pulmonary Fibrosis - genetics / Pulmonary Fibrosis - metabolism / Pulmonary Fibrosis - pathology / Respiratory syncytial virus / Respiratory Syncytial Virus Infections / Respiratory Syncytial Virus Infections - metabolism / Respiratory Syncytial Virus Infections - pathology / Respiratory Syncytial Virus Infections - virology / Respiratory tract / Respiratory tract diseases / Stem Cells / Three dimensional models / Time Factors / Tissue Engineering / Tissue Engineering - methods / Transplantation / Xenotransplantation