ArticleCell death discovery2021
Human pluripotent stem-cell-derived alveolar organoids for modeling pulmonary fibrosis and drug testing.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Advancing lung organoids toward clinical applications: a global perspective on research focus and future directions.Frontiers in medicine · 2025Pooled it
- Lung Organoids: Systematic Review of Recent Advancements and its Future Perspectives.Tissue engineering and regenerative medicine · 2024Pooled it
- Engineering autoimmune disease models using organoids: Harnessing microenvironmental engineering for precision medicine and immunological recapitulation.Bioengineering & translational medicine · 2026Review
- Targeted DNA triplex-forming oligonucleotide liposome for pulmonary fibrosis gene therapy.Cell reports. Medicine · 2026Article
- RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis.Biomolecules · 2026Review
- Stage-adaptive integration of polydopamine promotes human pluripotent stem cell-derived alveolar organoids differentiation and maturation.Materials today. Bio · 2026Article
- Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.Nature communications · 2026Article
- Lung organoids and organ-on-a-chip models in respiratory disease research: advances, applications, and challenges.Respiratory research · 2026Review
- AI-enabled label free monitoring of TGFβ1-induced remodeling in iPSC-derived alveolar organoids.Materials today. Bio · 2026Article
- Milk fat globule EGF and factor V/VIII domain containing (MFGE8) as a novel player in equine endometrial fibrosis.Scientific reports · 2026Article
- Lung organoids as a human system for Mycobacteria infection modeling and drug testing.The FEBS journal · 2026Review
- Research Advances and Disease Modeling in Respiratory Organoids.Biomedicines · 2026Review
- Stem cell-based therapies for silicosis: mechanisms, sources, clinical translation, and emerging strategies.Frontiers in immunology · 2026Review
- Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models.International journal of molecular sciences · 2025Review
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids.International journal of stem cells · 2025Article
- Model Organoids: Integrated Frameworks for the Next Frontier of Healthcare Advancements.Stem cell reviews and reports · 2025Review
- Targeting USP11 counteractsTheranostics · 2025Article
- Immunological mechanisms underlying fibrotic diseases via single-cell technologies.Frontiers in immunology · 2025Review
- Culture and Characterization of Differentiated Airway Organoids from Fetal Mouse Lung Proximal Progenitors.Bio-protocol · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Detailed understanding of the pathogenesis and development of effective therapies for pulmonary fibrosis (PF) have been hampered by lack of in vitro human models that recapitulate disease pathophysiology. In this study, we generated alveolar organoids (AOs) derived from human pluripotent stem cells (hPSCs) for use as an PF model and for drug efficacy evaluation. Stepwise direct differentiation of hPSCs into alveolar epithelial cells by mimicking developmental cues in a temporally controlled manner was used to generate multicellular AOs. Derived AOs contained the expected spectrum of differentiated cells, including alveolar progenitors, type 1 and 2 alveolar epithelial cells and mesenchymal cells. Treatment with transforming growth factor (TGF-β1) induced fibrotic changes in AOs, offering a PF model for therapeutic evaluation of a structurally truncated form (NP-011) of milk fat globule-EGF factor 8 (MFG-E8) protein. The significant fibrogenic responses and collagen accumulation that were induced by treatment with TGF-β1 in these AOs were effectively ameliorated by treatment with NP-011 via suppression of extracellular signal-regulated kinase (ERK) signaling. Furthermore, administration of NP-011 reversed bleomycin-induced lung fibrosis in mice also via ERK signaling suppression and collagen reduction. This anti-fibrotic effect mirrored that following Pirfenidone and Nintedanib administration. Furthermore, NP-011 interacted with macrophages, which accelerated the collagen uptake for eliminating accumulated collagen in fibrotic lung tissues. This study provides a robust in vitro human organoid system for modeling PF and assessing anti-fibrotic mechanisms of potential drugs and suggests that modified MGF-E8 protein has therapeutic potential for treating PF.
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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.