ArticleeLife2021
Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- Fibroblasts: a diverse population of cells balancing homeostasis, wound healing, regeneration, inflammation, fibrosis, and cancer across organs.JCI insight · 2026Review
- SIRT6 enhances the therapeutic potential of extracellular vesicles in mitigating osteoarthritis in rat models.Stem cell research & therapy · 2026Article
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Persistence of alveolar fibroblast-derived ADAMTS4+ cells in a preclinical model of delayed pulmonary fibrosis resolution.Nature communications · 2026Article
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Wnt signaling pathway in lung aging and aging-related chronic lung diseases.Biogerontology · 2025Review
- Epithelial-mesenchymal cell competition coordinates fate transitions across tissue compartments during lung development and fibrosis.Nature communications · 2025Article
- Mechanisms and markers of lung ageing in health and disease.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Enhanced application potential of alveolar organoids through epithelial and niche cell interactions.Scientific reports · 2025Article
- Reactivation of CTLA4-expressing T cells accelerates resolution of lung fibrosis in a humanized mouse model.The Journal of clinical investigation · 2025Article
- Article
- Evidence for a lipofibroblast-to-The European respiratory journal · 2025Article
- Lipids to the Rescue in Pulmonary Fibrosis: Biosynthesis, Bioenergetics, or Epigenetics?American journal of respiratory cell and molecular biology · 2024Article
- Transcriptomics Analysis Identifies the Decline in the Alveolar Type II Stem Cell Niche in Aged Human Lungs.American journal of respiratory cell and molecular biology · 2024Article
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- Article
- Cellular Senescence: A Troy Horse in Pulmonary Fibrosis.International journal of molecular sciences · 2023Review
- Alveolar epithelial regeneration in the aging lung.The Journal of clinical investigation · 2023Review
- Aged mesenchymal stem cells and inflammation: from pathology to potential therapeutic strategies.Biology direct · 2023Review
- The lung mesenchyme in development, regeneration, and fibrosis.The Journal of clinical investigation · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or 'alveolospheres' with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology.
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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.