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Updated: Jun 14, 2026
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Preparation of Plasma Membrane Vesicles from Bone Marrow Mesenchymal Stem Cells for Potential Cytoplasm Replacement Therapy
Published on: May 18, 2017
Combatting ventilator induced diaphragm dysfunction with human bone marrow mesenchymal stromal cell-derived
Ya Wen1, Xiang Zhang2, Yvette Hedström1,3
1Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
Skeletal Muscle
|June 13, 2026
Summary
Prolonged mechanical ventilation causes lung injury and diaphragm dysfunction. Human bone marrow-derived mesenchymal stem cell extracellular vesicles (EVs) simultaneously improved lung pathology and diaphragm function in a rat model, offering a promising intervention.
Area of Science:
- Critical Care Medicine
- Regenerative Medicine
- Pulmonology
Background:
- Prolonged mechanical ventilation is linked to ventilator-induced lung injury (VILI) and ventilator-induced diaphragm dysfunction (VIDD).
- These parallel conditions worsen patient outcomes, prolonging intensive care unit (ICU) stays and delaying weaning.
- A novel rat experimental ICU (ExICU) model was used to investigate simultaneous lung and diaphragm abnormalities.
Purpose of the Study:
- To evaluate the efficacy of human bone marrow-mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (EVs) in treating VILI and VIDD.
- To assess the potential of EVs to concurrently alleviate lung and diaphragm damage in a preclinical model.
- To explore the molecular mechanisms underlying the protective effects of EVs.
Main Methods:
- Rats underwent 5 days of controlled mechanical ventilation in an ExICU model.
- A single intravenous dose of BM-MSC-derived EVs was administered to a treatment group.
- Assessments included lung histopathology, diaphragm contractile function, and multi-omics analyses (transcriptomics, metabolomics, proteomics) of lung, diaphragm, and bronchoalveolar lavage fluid (BALF).
Main Results:
- Mechanical ventilation led to significant lung damage and a ~50% reduction in diaphragm fiber size and specific force.
- EV treatment demonstrated parallel improvements in both lung pathology and diaphragm contractile function.
- Multi-omics data revealed coordinated molecular changes in lung, BALF, and diaphragm post-ventilation, largely reversed by EV administration.
Conclusions:
- A strong association exists between lung injury and diaphragm dysfunction during extended mechanical ventilation.
- BM-MSC-derived EVs exhibit parallel protective effects on both the lungs and diaphragm.
- EVs represent a potential therapeutic strategy to mitigate mechanical ventilation-related complications in critically ill patients.