ArticleRespiratory research2024
The use of cultured human alveolar basal cells to mimic honeycomb formation in idiopathic pulmonary fibrosis.
Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Conditional BCL-2 Expression in Fibroblasts Promotes Persistent Pulmonary Fibrosis which is Reversible by Therapeutic BCL-2 Inhibition.Nature communications · 2026Article
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Insight into the pathogenesis of interstitial lung diseases and near-to-native lung fibrosis models.European journal of medical research · 2025Review
- Characteristics of ectopic alveolar basal cells relative to airway basal cells in fibrosis.ERJ open research · 2025Article
- Collagen VII Is Associated with Airway Remodeling, Honeycombing, and Fibroblast Foci in Usual Interstitial Pneumonia/Idiopathic Pulmonary Fibrosis.The American journal of pathology · 2025Article
- Tissue-Informed Biomaterial Innovations Advance Pulmonary Regenerative Engineering.ACS macro letters · 2025Review
- The pathogenesis of idiopathic pulmonary fibrosis: from "folies à deux" to "Culprit cell Trio".Pathologica · 2025Article
- Advances in the research and application of stem cell therapies for idiopathic pulmonary fibrosis.American journal of clinical and experimental immunology · 2025Review
- In Vitro Modeling of Idiopathic Pulmonary Fibrosis: Lung-on-a-Chip Systems and Other 3D Cultures.International journal of molecular sciences · 2024Review
- Lung organoids as emerging models in idiopathic pulmonary fibrosis research: Current applications, challenges, and future directions.Therapeutic advances in respiratory diseaseReview
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundHoneycomb cysts (HC) within the alveolar region are distinct histopathological features in the lungs of idiopathic pulmonary fibrosis (IPF) patients. HC are lined with a single-or stratified layer of basal cells (BC), or with a bronchiolar-like epithelium composed of basal-, ciliated- and secretory epithelial cells. By using cultured IPF patient-derived alveolar BC, we aimed to establish an in vitro- and in vivo model to mimic HC formation in IPF. We (1) optimized conditions to culture and propagate IPF patient-derived alveolar BC, (2) cultured the cells on an air liquid interface (ALI) or in a three dimensional (3D) organoid model, and (3) investigated the cells` behavior after instillation into bleomycin-challenged mice.
methodsAlveolar BC were cultured from peripheral IPF lung tissue and grown on tissue-culture treated plastic, an ALI, or in a 3D organoid model. Furthermore, cells were instilled into bleomycin-challenged NRG mice. Samples were analyzed by TaqMan RT-PCR, immunoblotting, immunocytochemistry/immunofluorescence (ICC/IF), or immunohistochemistry (IHC)/IF. Mann-Whitney tests were performed using GraphPad Prism software.
resultsCultured alveolar BC showed high expression of canonical basal cell markers (TP63, keratin (KRT)5, KRT14, KRT17), robust proliferation, and wound closure capacity. The cells could be cryopreserved and propagated for up to four passages without a significant loss of basal cell markers. When cultured on an ALI or in a 3D organoid model, alveolar BC differentiated to ciliated- and secretory epithelial cells. When instilled into bleomycin-challenged mice, human alveolar BC cells formed HC-like structures composed of human basal-, and secretory epithelial cells within the mouse parenchyma.
conclusionIPF patient-derived alveolar BC on an ALI, in 3D organoids or after instillation into bleomycin-challenged mice form HC-like structures that closely resemble HC within the IPF lung. These models therefore represent powerful tools to study honeycomb formation, and its potential therapeutic inhibition in IPF.
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