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MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model
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 combatt...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814377/ https://www.ncbi.nlm.nih.gov/pubmed/33468250 http://dx.doi.org/10.1186/s13287-021-02143-w |
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author | Kaspi, Haggai Semo, Jonathan Abramov, Nathalie Dekel, Chen Lindborg, Stacy Kern, Ralph Lebovits, Chaim Aricha, Revital |
author_facet | Kaspi, Haggai Semo, Jonathan Abramov, Nathalie Dekel, Chen Lindborg, Stacy Kern, Ralph Lebovits, Chaim Aricha, Revital |
author_sort | Kaspi, Haggai |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7814377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78143772021-01-18 MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model Kaspi, Haggai Semo, Jonathan Abramov, Nathalie Dekel, Chen Lindborg, Stacy Kern, Ralph Lebovits, Chaim Aricha, Revital Stem Cell Res Ther Research 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. BioMed Central 2021-01-19 /pmc/articles/PMC7814377/ /pubmed/33468250 http://dx.doi.org/10.1186/s13287-021-02143-w Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kaspi, Haggai Semo, Jonathan Abramov, Nathalie Dekel, Chen Lindborg, Stacy Kern, Ralph Lebovits, Chaim Aricha, Revital MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model |
title | MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model |
title_full | MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model |
title_fullStr | MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model |
title_full_unstemmed | MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model |
title_short | MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model |
title_sort | msc-ntf (nurown®) exosomes: a novel therapeutic modality in the mouse lps-induced ards model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814377/ https://www.ncbi.nlm.nih.gov/pubmed/33468250 http://dx.doi.org/10.1186/s13287-021-02143-w |
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