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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Apr 13

PMID 37047264

Authors

Anna Demchenko

Ekaterina Kondrateva

Vyacheslav Tabakov

Anna Efremova

Diana Salikhova

Tatiana Bukharova

Dmitry Goldshtein

Maxim Balyasin

Natalia Bulatenko

Elena Amelina

Alexander Lavrov

Svetlana Smirnikhina

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Human Induced Lung Organoids: A Promising Tool for Cystic Fibrosis Drug Screening.

Demchenko A, Balyasin M, Nazarova A, Grigorieva O, Panchuk I, Kondrateva E Int J Mol Sci. 2025; 26(2).

PMID: 39859153 PMC: 11764749. DOI: 10.3390/ijms26020437.

Airway basal cells from human-induced pluripotent stem cells: a new frontier in cystic fibrosis research.

Demchenko A, Belova L, Balyasin M, Kochergin-Nikitsky K, Kondrateva E, Voronina E Front Cell Dev Biol. 2024; 12:1336392.

PMID: 38737127 PMC: 11082282. DOI: 10.3389/fcell.2024.1336392.

Alveolar Organoids in Lung Disease Modeling.

Purev E, Bahmed K, Kosmider B Biomolecules. 2024; 14(1).

PMID: 38254715 PMC: 10813493. DOI: 10.3390/biom14010115.

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