ArticleProceedings of the National Academy of Sciences of the United States of America2016
Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Stem cell therapy in COVID-19: Pooled evidence from SARS-CoV-2, SARS-CoV, MERS-CoV and ARDS: A systematic review.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Pooled it
- Treatment with Allogeneic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multicenter Phase 2b Clinical Trial (STAT).American journal of respiratory and critical care medicine · 2026Trial
- Mesenchymal stem cells for the adjunctive treatment of cytomegalovirus pneumonia in hematopoietic stem cell transplant recipients: a Single-center prospective study.Annals of hematology · 2025Trial
- A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.American journal of respiratory and critical care medicine · 2023Trial
- Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.Signal transduction and targeted therapy · 2021Trial
- Assessment of influenza virus and coronavirus tropism, replication competence and disease severity inThe Journal of general virology · 2026Article
- Acute Lung Injury Induced by Hyperbaric Oxygen or Other External Factors, with a Focus on Exosomes.International journal of molecular sciences · 2026Review
- Mesenchymal stem cells in sepsis-induced organ dysfunction: mechanisms and therapeutic potential.Stem cell research & therapy · 2025Review
- Lung cell fates during influenza.Cell research · 2025Review
- Comprehensive and translational pathobiology of COVID-19 based on cellular and molecular techniques.Practical laboratory medicine · 2025Review
- Mitochondrial Antiviral Signaling Protein Activation by Retinoic Acid-Inducible Gene I Agonist Triggers Potent Antiviral Defense in Umbilical Cord Mesenchymal Stromal Cells Without Compromising Mitochondrial Function.International journal of molecular sciences · 2025Article
- Mechanisms of impaired alveolar fluid clearance.Anatomical record (Hoboken, N.J. : 2007) · 2025Review
- Cell therapies for viral diseases: a new frontier.Seminars in immunopathology · 2025Review
- Mesenchymal stem cells and their extracellular vesicle therapy for neurological disorders: traumatic brain injury and beyond.Frontiers in neurology · 2025Review
- miRNA-431-5p enriched in EVs derived from IFN-β stimulated MSCs potently inhibited ZIKV through CD95 downregulation.Stem cell research & therapy · 2024Article
- Recent progress in mesenchymal stem cell-based therapy for acute lung injury.Cell and tissue banking · 2024Review
- Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS.Frontiers in immunology · 2024Article
- The pathogenesis of influenza in intact alveoli: virion endocytosis and its effects on the lung's air-blood barrier.Frontiers in immunology · 2024Review
- Extracellular Vesicles as a Translational Approach for the Treatment of COVID-19 Disease: An Updated Overview.Viruses · 2023Review
- Pooled evidence from preclinical and clinical studies for stem cell-based therapy in ARDS and COVID-19.Molecular and cellular biochemistry · 2023Review
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.
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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.