Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19

Autor: Roger M. Ilagan, Sarah Hogan, Lauren Rochelle, Michaela Welch, Caryn Cloer, Kelly Tan, Laila Roudsari, Thomas Petersen, Joseph L. Charest, Li Fugang, Timothy Petrie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
RNA viruses
Male
Viral Diseases
Physiology
Coronaviruses
THP-1 Cells
medicine.medical_treatment
Cancer Treatment
Biochemistry
Rats
Sprague-Dawley
Medical Conditions
Immune Physiology
Medicine and Health Sciences
Medicine
Immune Response
Pathology and laboratory medicine
Phospholipids
Innate Immune System
Multidisciplinary
Cytokine Therapy
Medical microbiology
Lipids
Infectious Diseases
Cytokine
Oncology
Viruses
Cytokines
Angiotensin-Converting Enzyme 2
SARS CoV 2
Pathogens
Cellular Structures and Organelles
Signal transduction
medicine.symptom
Research Article
Signal Transduction
Stromal cell
SARS coronavirus
Science
Immunology
Acute Lung Injury
Inflammation
Lung injury
Microbiology
Models
Biological
Immunomodulation
Extracellular Vesicles
Signs and Symptoms
Animals
Humans
Vesicles
Secretion
SARS-CoV-2
business.industry
Mesenchymal stem cell
Organisms
Viral pathogens
Biology and Life Sciences
COVID-19
Covid 19
Mesenchymal Stem Cells
Cell Biology
Pneumonia
Molecular Development
Microbial pathogens
Disease Models
Animal
Immune System
Cancer research
Cytokine secretion
Clinical Medicine
Physiological Processes
business
Developmental Biology
Zdroj: PLoS ONE, Vol 16, Iss 11 (2021)
PLoS ONE, Vol 16, Iss 11, p e0259732 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.
Databáze: OpenAIRE
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