Journal
STEM CELLS
Volume 39, Issue 10, Pages 1310-1321Publisher
OXFORD UNIV PRESS
DOI: 10.1002/stem.3422
Keywords
cytokines; induced pluripotent stem cells; interleukins (ILs); lung
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/V01126X/1, V011278/1]
- H2020 Marie Sklodowska-Curie Actions [721975]
- Medical Research Council
- National Institute for Health Research [NIHR2000907, R21AI138074]
- URKI [20197]
- Royal Society [RSWF\R1\180013]
- Liverpool School of Tropical Medicine [V017772]
- BBSRC [BB/V01126X/1] Funding Source: UKRI
Ask authors/readers for more resources
This study developed a simplified protocol for generating airway epithelial basal-like cells from induced pluripotent stem cells, which mimic the upper airway epithelium and support viral infection and cytokine secretion. This method provides a feasible upper airway model for respiratory disease therapy development and assessment of drug toxicity on human lungs.
As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal-like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal-like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air-liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS-CoV-2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available