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Review
. 2024 Jan 16;14(1):115.
doi: 10.3390/biom14010115.

Alveolar Organoids in Lung Disease Modeling

Enkhee Purev  1   2 , Karim Bahmed  1   2   3 , Beata Kosmider  1   2   3   4
Affiliations
Review

Alveolar Organoids in Lung Disease Modeling

Enkhee Purev et al. Biomolecules. .

Abstract

Lung organoids display a tissue-specific functional phenomenon and mimic the features of the original organ. They can reflect the properties of the cells, such as morphology, polarity, proliferation rate, gene expression, and genomic profile. Alveolar type 2 (AT2) cells have a stem cell potential in the adult lung. They produce and secrete pulmonary surfactant and proliferate to restore the epithelium after damage. Therefore, AT2 cells are used to generate alveolar organoids and can recapitulate distal lung structures. Also, AT2 cells in human-induced pluripotent stem cell (iPSC)-derived alveolospheres express surfactant proteins and other factors, indicating their application as suitable models for studying cell-cell interactions. Recently, they have been utilized to define mechanisms of disease development, such as COVID-19, lung cancer, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this review, we show lung organoid applications in various pulmonary diseases, drug screening, and personalized medicine. In addition, stem cell-based therapeutics and approaches relevant to lung repair were highlighted. We also described the signaling pathways and epigenetic regulation of lung regeneration. It is critical to identify novel regulators of alveolar organoid generations to promote lung repair in pulmonary diseases.

Keywords: AT2 cells; alveolar organoids; diseases; lung; regeneration.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lung microenvironment. Basal, ciliated, tuft, club, and goblet cells were identified. Pulmonary neuroendocrine cells (PNEC), pericytes, ionocytes, alveolar macrophages (AM), fibroblasts, mesenchymal stem cells (MSC), and endothelial cells (EC) are also present. The distal lung alveoli include alveolar type 2 (AT2) cells, which differentiate to alveolar type 1 (AT1) cells.
Figure 2
Figure 2
A schematic illustration of signaling pathways in lung regeneration. An induction of distal-like organoids using effective FGF ligands. Wnt-producing fibroblasts contribute to regulating stem cell features of AT2 cells. Damage-associated transient progenitors induced by IL-1β-driven Hif1α participate in alveolar regeneration and AT1 differentiation. AT2 cells can transdifferentiate into Krt5+ basal cells when co-cultured with adult human lung mesenchyme cells. Supplementation with recombinant HHIP decreased KRT5 and increased SFTPC expression. Hh transcription factor, GLI1, was attenuated and increased BMP ligands. In this organoid system, AT2-derived basal cells express basal markers such as SOX2, NGFR, and TP63. TGF-β-induced myofibroblast differentiation diminishes the lung epithelial repair.
Figure 3
Figure 3
Applications of lung organoids. Lung organoids can be utilized to study anti-cancer, antiviral, and antimicrobial drugs. Personalized medicine provides a unique value in the applications of lung organoids. They have been used to model lung diseases such as lung cancer, COPD, and IPF. Also, lung organoids are applied to study host-pathogen interactions.
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