Generation of an alveolar epithelial type II cell line from induced pluripotent stem cells.

Tamò, Luca; Hibaoui, Youssef; Kallol, Sampada; Alves, Marco P.; Albrecht, Christiane; Hostettler, Katrin E; Feki, Anis; Rougier, Jean-Sébastien; Abriel, Hugues; Knudsen, Lars; Gazdhar, Amiq; Geiser, Thomas (2018). Generation of an alveolar epithelial type II cell line from induced pluripotent stem cells. American journal of physiology - lung cellular and molecular physiology, 315(6), L921-L932. American Physiological Society 10.1152/ajplung.00357.2017

[img] Text
ajplung.00357.2017.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

Differentiation of primary alveolar type II epithelial cells (AEC type II) to AEC type I in culture is a major barrier in the study of the alveolar epithelium in vitro. The establishment of an AEC type II cell line derived from induced pluripotent stem cells (iPSC) represents a novel opportunity to study alveolar epithelial cell biology, for instance in the context of lung injury, fibrosis and repair. In the present study, we generated long lasting AECII from iPSC (iPSC-AEC). Long lasting iPSC-AECII (LL)-iPSC-AECII) displayed morphological characteristics of AECII including growth in a cobble stone monolayer, the presence of lamellar bodies and microvilli as shown by electron microscopy. Also, (LL)-iPSC-AECII expressed AEC type II proteins such as cytokeratin, surfactant protein C and lysotracker DND 26 (a marker for lamellar bodies). Furthermore, the (LL)-iPSC-AECII exhibited functional properties of AECII by an increase of transepithelial electrical resistance (TERR) over time, secretion of inflammatory mediators in biologically relevant quantities (interleukin-6, interleukin-8) and efficient in vitro alveolar epithelial wound repair. Consistent with the AECII phenotype, the cell line showed the ability to uptake and release surfactant protein B, to secrete phospholipids and to differentiate into AEC type I. In summary, we established a long lasting, but finite AEC type II cell line derived from iPSC as a novel cellular model to study alveolar epithelial cell biology in lung health and disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Tamò, Luca Giuseppe Athos; Kallol, Sampada Arvindrao; Alves, Marco; Albrecht, Christiane; Rougier, Jean-Sébastien; Abriel, Hugues; Gazdhar, Amiq and Geiser, Thomas

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1040-0605

Publisher:

American Physiological Society

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

17 Jan 2019 15:07

Last Modified:

09 Feb 2019 01:32

Publisher DOI:

10.1152/ajplung.00357.2017

PubMed ID:

30211653

Uncontrolled Keywords:

AEC differentiation AECII disease modelling induced pluripotent stem cells lung regeneration

BORIS DOI:

10.7892/boris.123219

URI:

https://boris.unibe.ch/id/eprint/123219

Actions (login required)

Edit item Edit item
Provide Feedback