Abstract
BackgroundOne 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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.
Highlights
One of the most severe complications of the current COVID-19 pandemic is acute respiratory distress syndrome (ARDS)
Compared to cellular treatment, MSCderived exosomes are inherently safer for intratracheal administration and have several advantages, such as low immunogenicity, high stability, no potential to transdifferentiate into a different cell type, and enhanced tissue penetration capabilities [9]
Mesenchymal stem cells (MSC) were induced to differentiate into MSC-NTF cells using a mediumbased approach in which cells were incubated in a medium containing 1 mM dibutyryl cyclic AMP, 20 ng/ml human basic fibroblast growth factor, 5 ng/ml human platelet-derived growth factor (PDGFAA), and 50 ng/ml human Heregulin β1
Summary
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. Mesenchymal stem cells (MSCs) have been suggested as a potential treatment for ARDS due to their significant immunomodulatory properties. Acute respiratory distress syndrome (ARDS) is the most common and severe complication of the current COVID-19 pandemic [1]. In ARDS, an accumulation of inflammatory cells in the lungs releases large amounts of pro-inflammatory cytokines, known as a cytokine storm, causing widespread inflammation, pulmonary damage, loss of lung function, and death [2, 3]. A small clinical trial of COVID-19 patients treated with MSC exosomes has shown that one treatment increased patient oxygenation, reduced the immune response, and increased anti-inflammatory cytokine levels [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
