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MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model.
Stem Cell Res Ther. 2021 01 19; 12(1):72.SC

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.

Authors+Show Affiliations

Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA.Brainstorm Cell Therapeutics, Ltd., 1325 Avenue of Americas, New York City, NY, 10019, USA. raricha@brainstorm-cell.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33468250

Citation

Kaspi, Haggai, et al. "MSC-NTF (NurOwn®) Exosomes: a Novel Therapeutic Modality in the Mouse LPS-induced ARDS Model." Stem Cell Research & Therapy, vol. 12, no. 1, 2021, p. 72.
Kaspi H, Semo J, Abramov N, et al. MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model. Stem Cell Res Ther. 2021;12(1):72.
Kaspi, H., Semo, J., Abramov, N., Dekel, C., Lindborg, S., Kern, R., Lebovits, C., & Aricha, R. (2021). MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model. Stem Cell Research & Therapy, 12(1), 72. https://doi.org/10.1186/s13287-021-02143-w
Kaspi H, et al. MSC-NTF (NurOwn®) Exosomes: a Novel Therapeutic Modality in the Mouse LPS-induced ARDS Model. Stem Cell Res Ther. 2021 01 19;12(1):72. PubMed PMID: 33468250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MSC-NTF (NurOwn®) exosomes: a novel therapeutic modality in the mouse LPS-induced ARDS model. AU - Kaspi,Haggai, AU - Semo,Jonathan, AU - Abramov,Nathalie, AU - Dekel,Chen, AU - Lindborg,Stacy, AU - Kern,Ralph, AU - Lebovits,Chaim, AU - Aricha,Revital, Y1 - 2021/01/19/ PY - 2020/10/05/received PY - 2021/01/05/accepted PY - 2021/1/20/entrez PY - 2021/1/21/pubmed PY - 2021/1/26/medline KW - Acute respiratory distress syndrome KW - COVID-19 KW - Exosomes KW - Lung injury KW - Mesenchymal stem cells SP - 72 EP - 72 JF - Stem cell research & therapy JO - Stem Cell Res Ther VL - 12 IS - 1 N2 - 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. SN - 1757-6512 UR - https://www.unboundmedicine.com/medline/citation/33468250/MSC_NTF__NurOwn®__exosomes:_a_novel_therapeutic_modality_in_the_mouse_LPS_induced_ARDS_model_ L2 - https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02143-w DB - PRIME DP - Unbound Medicine ER -