Efficient generation of lung and airway epithelial cells from human pluripotent stem cells

Developers

Sarah X L Huang, Mohammad Naimul Islam, Jahar Bhattacharya, Hans-Willem Snoeck, etc.

Description of the technology

The authors of the technology 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 their 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. This protocol generates most cell types of the respiratory system, so it may be useful for deriving patient-specific therapeutic cells.

Practical application

The technology is developed to generate lung and airway epithelial cells from human pluripotent stem cells (hPSCs), so it would have applications in regenerative medicine, modeling of lung disease, drug screening and studies of human lung development.

This protocol yields most cell types of the respiratory system, so it will allow studies of lineage determination. Besides, this technology may help to address a central problem in lung tissue engineering using autologous iPSC-derived cells, i.e., to generate sufficient numbers of cells with the appropriate variety and ratio of epithelial cells and their progenitors normally found in the lung.

The technology opens up the possibility to generate type II alveolar epithelial cells (ATII) from hPSCs, so it can be applicable for modeling of diseases such as congenital surfactant deficiency syndromes. Besides, ATII cells have recently been identified as alveolar stem cells and may be at the origin of lung adenocarcinoma. Thus, the technology could be useful for constructing the models of lung diseases in vivo and in vitro.

Laboratories

• Columbia Center for Translational Immunology, Columbia University Medical Center, New York {USA)
• Department of Medicine, Columbia University Medical Center, New York {USA)
• Department of Physiology & Cellular Biophysics, Columbia University Medical Center, New York {USA)
• Department of Microbiology and Immunology, Columbia University Medical Center, New York {USA)

Links

Publications

• Huang, S.X. et al. «Efficient generation of lung and airway epithelial cells from human pluripotent stem cells." 32.1 Nat Biotechnol. (2014): 84−91.
• Huang, S.X. et al. «The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells." 10.3 Nat Protoc. (2015): 413−425.
• Green, M.D., Huang, S.X., Snoeck, H.W. «Stem cells of the respiratory system: from identification to differentiation into functional epithelium." 35.4 Bioessays. (2013): 261−270.