MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model
Open accessAbstract
Background: One of the most severe complications of the current COVID-19 pandemic is acute respiratory distress syndrome (ARDS). ARDS is caused by increased amounts of pro-inflammatory cytokines, leading to lung damage and loss of lung function. There are currently no effective therapies for combatting ARDS. Mesenchymal stem cells (MSCs) have been suggested as a potential treatment for ARDS due to their significant immunomodulatory properties. MSC small extracellular vesicles (sEVs), including exosomes, modulate the immune response as effectively as MSCs themselves, with the added advantages of increased safety and tissue penetration. Methods: We isolated sEVs from MSCs induced to secrete increased levels of neurotrophic and immunomodulatory factors, termed Exo MSC-NTF, and compared their ability to treat ARDS, in a lung injury LPS mouse model, to sEVs isolated from naïve MSCs (Exo MSC). Measurments of lung histopathological changes and neutrophil infiltration, blood oxygen saturation, and bronchoalveolar lavge fluid (BALF) proinflammatory cytokines and coagulation related factors were performed. Results: We found that Exo MSC-NTF was superior to Exo MSC in reducing LPS-induced ARDS markers, including physiological lung damage such as alveolar wall thickness, fibrin presence, and neutrophil accumulation, as well as increasing oxygenation levels. Furthermore, Exo MSC-NTF reversed the imbalance in the host immune response, seen as decreased IFN-γ, IL-6, TNF-α, and RANTES levels in the bronchoalveolar lavage fluid. Conclusions: These positive preclinical results suggest that Exo MSC-NTF may be suitable as a therapy for COVID-19-induced ARDS and are more effective at combatting ARDS physiological, pathological, and biochemical symptoms than sEVs isolated from non-induced MSCs.
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MSC-derived exosomes have broad-spectrum therapeutic efficacy validated in multiple disease models.
“the broad-spectrum therapeutic efficacy of MSC-derived exosomes have also been validated in multiple disease models, including carbon tetrachloride (CCl4)-induced liver injury [16], myocardial ischemia/reperfusion injury [17], LPS-induced acute respiratory distress syndrome [18], and graft-versus-host disease [19].”
From A tailored bioactive 3D porous poly(lactic-acid)-exosome scaffold with osteo-immunomodulatory and osteogenic differentiation properties (2022) · cites this paper as [18]
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- Authors
- Kaspi, H., Semo, J., Abramov, N., Dekel, C., Lindborg, S., Kern, R., Lebovits, C., & Aricha, R.
- Corresponding author
- Aricha, Revital
- Venue
- Stem Cell Research & Therapy
- Published
- 2021-01-19
- Volume
- 12
- Issue
- 1
- Pages
- 72-72
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC7814377
- OpenAlex
- W3123094951
- Cited by
- 68
- References
- 37
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 12 · 2023: 17 · 2022: 12 · 2021: 5
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- acute respiratory distress syndrome, mesenchymal stem cell-derived exosomes, small extracellular vesicles, lipopolysaccharide-induced lung injury, COVID-19 pandemic, inflammatory cytokines, neutrophil infiltration, immunomodulation, oxygenation, bronchoalveolar lavage fluid, coagulation factors, interferon-gamma, interleukin-6, TNF-α, RANTES
- MeSH terms
- Animals, Disease Models, Animal, Female, Humans, Lipopolysaccharides, Respiratory Distress Syndrome, Mesenchymal Stem Cell Transplantation, Mice, Exosomes, Immunomodulation, Mesenchymal Stem Cells
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