1. Generation of an immortalized functional alveolar epithelial cell line originating from human induced pluripotent stem cells
- Author
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Sampada Kallol, Youssef Hibaoui, Luca Tamò, Christiane Albrecht, Anis Feki, Amiq Gazdhar, Thomas Geiser, and Marco P. Alves
- Subjects
Cytokeratin ,Tissue engineering ,Cell culture ,education ,Immunology ,Tumor necrosis factor alpha ,Surfactant protein C ,Telomerase reverse transcriptase ,respiratory system ,Lamellar granule ,Biology ,Induced pluripotent stem cell ,Cell biology - Abstract
The establishment of an alveolar epithelial cell (AEC) line derived from induced pluripotent stem cells (iPSC) represents a novel opportunity in lung disease modelling and tissue engineering. In the present study, we succeeded in generating type II AECs from iPSCs. To ensure homogeneous and long term propagation of these cells, iPSC-derived type II AECs, were immortalized by human telomerase reverse transcriptase andpolycomb complex protein BMI-1 lentiviral vectors. The generated type II AEC line displayed morphological characteristics of type II AECs including growing as a cobble stone monolayer. Thus, electron microscopy analysis of this cell line confirmed the presence of lamellar body and microvilli. Also this cell line expressed type II AEC proteins such as cytokeratin, surfactant protein C and lysotracker DND 26 (marker for lamellar body). Furthermore, the type II AEC line exhibited functional properties of type II AECs including an increase of their transepithelial electrical resistance over time and an improved wound closure in presence of serum in the invitro wound healing assay. Upon TNF-α stimulation, these cells released IL-6 an IL-8 cytokines. Consistent with type II AEC phenotype, the cell line showed the ability to uptake and release of surfactant protein B and to differentiate towards type I AECs. Altogether, this study established immortalized type II AECs derived from iPSCs as a novel cellular model for lung disease modelling and tissue engineering.
- Published
- 2016