ArticleStem cell research & therapy2024
Influence of mesenchymal and biophysical components on distal lung organoid differentiation.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Pulmonary organoid models demonstrate compositionally driven epithelial plasticity and immune polarization.iScience · 2026Article
- Mechanochemical regulation of organoid morphogenesis: Integrated signaling circuits in engineered microenvironments.Materials today. Bio · 2026Review
- The mechanical microenvironment and lung stem cell fate.Frontiers in cell and developmental biology · 2026Review
- In vitro biomimetic models for respiratory diseases: progress in lung organoids and lung-on-a-chip.Stem cell research & therapy · 2025Review
- Upscaling: efficient generation of human lung organoids from induced pluripotent stem cells using a stirring bioreactor.Frontiers in bioengineering and biotechnology · 2025Article
- 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
9 authors.
Funding
Abstract
backgroundChronic lung disease of prematurity, called bronchopulmonary dysplasia (BPD), lacks effective therapies, stressing the need for preclinical testing systems that reflect human pathology for identifying causal pathways and testing novel compounds. Alveolar organoids derived from human pluripotent stem cells (hPSC) are promising test platforms for studying distal airway diseases like BPD, but current protocols do not accurately replicate the distal niche environment of the native lung. Herein, we investigated the contributions of cellular constituents of the alveolus and fetal respiratory movements on hPSC-derived alveolar organoid formation.
methodsHuman PSCs were differentiated in 2D culture into lung progenitor cells (LPC) which were then further differentiated into alveolar organoids before and after removal of co-developing mesodermal cells. LPCs were also differentiated in Transwell® co-cultures with and without human fetal lung fibroblast. Forming organoids were subjected to phasic mechanical strain using a Flexcell® system. Differentiation within organoids and Transwell® cultures was assessed by flow cytometry, immunofluorescence, and qPCR for lung epithelial and alveolar markers of differentiation including GATA binding protein 6 (GATA 6), E-cadherin (CDH1), NK2 Homeobox 1 (NKX2-1), HT2-280, surfactant proteins B (SFTPB) and C (SFTPC).
resultsWe observed that co-developing mesenchymal progenitors promote alveolar epithelial type 2 cell (AEC2) differentiation within hPSC-derived lung organoids. This mesenchymal effect on AEC2 differentiation was corroborated by co-culturing hPSC-NKX2-1
conclusionOur data suggest that biophysical and mesenchymal components promote AEC2 differentiation within hPSC-derived distal organoids in vitro.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.