MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model
Abstract 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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-021-02143-w |
| _version_ | 1819055145090023424 |
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| author | Haggai Kaspi Jonathan Semo Nathalie Abramov Chen Dekel Stacy Lindborg Ralph Kern Chaim Lebovits Revital Aricha |
| author_facet | Haggai Kaspi Jonathan Semo Nathalie Abramov Chen Dekel Stacy Lindborg Ralph Kern Chaim Lebovits Revital Aricha |
| author_sort | Haggai Kaspi |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T13:02:51Z |
| format | Article |
| id | doaj.art-5f2df5139e8b484c9086c902f89b0bca |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T13:02:51Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-5f2df5139e8b484c9086c902f89b0bca2022-12-21T19:03:07ZengBMCStem Cell Research & Therapy1757-65122021-01-0112111010.1186/s13287-021-02143-wMSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS modelHaggai Kaspi0Jonathan Semo1Nathalie Abramov2Chen Dekel3Stacy Lindborg4Ralph Kern5Chaim Lebovits6Revital Aricha7Brainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsBrainstorm Cell TherapeuticsAbstract 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.https://doi.org/10.1186/s13287-021-02143-wExosomesAcute respiratory distress syndromeCOVID-19Mesenchymal stem cellsLung injury |
| spellingShingle | Haggai Kaspi Jonathan Semo Nathalie Abramov Chen Dekel Stacy Lindborg Ralph Kern Chaim Lebovits Revital Aricha MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model Stem Cell Research & Therapy Exosomes Acute respiratory distress syndrome COVID-19 Mesenchymal stem cells Lung injury |
| 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 r exosomes a novel therapeutic modality in the mouse lps induced ards model |
| topic | Exosomes Acute respiratory distress syndrome COVID-19 Mesenchymal stem cells Lung injury |
| url | https://doi.org/10.1186/s13287-021-02143-w |
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