Airway and Lung Organoids from Human-Induced Pluripotent Stem Cells Can Be Used to Assess CFTR Conductance

Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell-cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining or...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-03, Vol.24 (7), p.6293
Main Authors: Demchenko, Anna, Kondrateva, Ekaterina, Tabakov, Vyacheslav, Efremova, Anna, Salikhova, Diana, Bukharova, Tatiana, Goldshtein, Dmitry, Balyasin, Maxim, Bulatenko, Natalia, Amelina, Elena, Lavrov, Alexander, Smirnikhina, Svetlana
Format: Article
Language:English
Subjects:
Analysis
Biopsy
Cell culture
CFTR
Colforsin - pharmacology
Computer software industry
Cystic fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cytoplasm
differentiation
Drug screening
Epithelial Cells
Epithelium
Forskolin
Human influences
human-induced pluripotent stem cells
Humans
Induced Pluripotent Stem Cells
Localization
Lung
Lung diseases
Medical research
Medicine, Experimental
Mutation
Organoids
Patients
Performance evaluation
Pluripotency
Regenerative medicine
Respiratory diseases
Respiratory tract
Scientific equipment and supplies industry
Stem cells
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Summary:Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell-cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids. We obtained airway and lung organoids from a healthy donor and from five donors with cystic fibrosis. Analysis of the cellular composition of airway and lung organoids showed that airway organoids contain proximal lung epithelial cells, while lung organoids contain both proximal and distal lung epithelial cells. Forskolin-induced swelling of organoids derived from a healthy donor showed that lung organoids, as well as airway organoids, contain functional epithelial cells and swell after 24 h exposure to forskolin, which makes it a suitable model for analyzing the cystic fibrosis transmembrane conductance regulator (CFTR) channel conductance in vitro. Thus, our results demonstrate the feasibility of generating and characterizing airway and lung organoids from hiPSCs, which can be used for a variety of future applications.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24076293