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Therapeutic Effects of Extracellular Vesicles Released from Bone Marrow, Adipose and Lung Tissue-Derived Mesenchymal Stem Cells in Experimental Sepsis
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A7405 - Therapeutic Effects of Extracellular Vesicles Released from Bone Marrow, Adipose and Lung Tissue-Derived Mesenchymal Stem Cells in Experimental Sepsis
Author Block: N. Blanco, N. Machado, L. Castro, F. F. Cruz, J. D. Silva, P. L. Silva, P. R. Rocco; Carlos Chagas Filho Institute of Biophysics, Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
RATIONALE: Sepsis is one of the most common causes of acute respiratory distress syndrome (ARDS) and is associated with severe systemic inflammation, causing damage to vital organs such as the heart and kidneys. Despite the use of antibiotics, morbidity and mortality remain high. Mesenchymal stem cells (MSCs) have proven effective in reducing inflammation and multiorgan injury while improving survival in mice, even when administered 6 hours after induction of polymicrobial sepsis in the cecal ligation and puncture (CLP) model. Previous studies have shown that higher doses of MSCs can reduce sepsis severity, but may result in embolism and stroke. Extracellular vesicles (EVs) derived from MSCs have advantages over MSC therapy: they are stable in the circulation without losing function (i.e., secrete a large number of therapeutic factors) and reduce the risk of embolism. In this context, we aimed to compare the effects of EVs obtained from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG)-derived MSCs on survival rate, lung inflammation, histology and mechanics in experimental sepsis. METHODS: In 24 C57Bl/6 mice (weight 20-25 g), sepsis was induced by CLP surgery. A sham-operated group was used as control (CTRL). Twenty-four hours after surgery, mice were assigned to receive saline or EVs from 3x106 BM-, AD-, or lung-derived MSCs. Forty-eight hours after surgery, survival rate, lung mechanics, and lung, liver, spleen, and kidney histology were evaluated. The total protein content of the EV fraction was quantified and the intensity and hydrodynamic diameter of EVs were measured and compared. RESULTS: BM-, AD-, and LUNG-derived EVs exhibited similar features. EVs improved survival rate and reduced static lung elastance, alveolar collapse, total number of cells, and neutrophils in alveolar septa regardless of source. CONCLUSION: In the CLP model of sepsis, BM-, AD-, and LUNG-derived EVs effectively reduce inflammation, thus improving lung histology and mechanics. EVs may hold promise for sepsis; however, further studies are required to elucidate the mechanisms of action of EVs from different sources.
Author Block: N. Blanco, N. Machado, L. Castro, F. F. Cruz, J. D. Silva, P. L. Silva, P. R. Rocco; Carlos Chagas Filho Institute of Biophysics, Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
RATIONALE: Sepsis is one of the most common causes of acute respiratory distress syndrome (ARDS) and is associated with severe systemic inflammation, causing damage to vital organs such as the heart and kidneys. Despite the use of antibiotics, morbidity and mortality remain high. Mesenchymal stem cells (MSCs) have proven effective in reducing inflammation and multiorgan injury while improving survival in mice, even when administered 6 hours after induction of polymicrobial sepsis in the cecal ligation and puncture (CLP) model. Previous studies have shown that higher doses of MSCs can reduce sepsis severity, but may result in embolism and stroke. Extracellular vesicles (EVs) derived from MSCs have advantages over MSC therapy: they are stable in the circulation without losing function (i.e., secrete a large number of therapeutic factors) and reduce the risk of embolism. In this context, we aimed to compare the effects of EVs obtained from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG)-derived MSCs on survival rate, lung inflammation, histology and mechanics in experimental sepsis. METHODS: In 24 C57Bl/6 mice (weight 20-25 g), sepsis was induced by CLP surgery. A sham-operated group was used as control (CTRL). Twenty-four hours after surgery, mice were assigned to receive saline or EVs from 3x106 BM-, AD-, or lung-derived MSCs. Forty-eight hours after surgery, survival rate, lung mechanics, and lung, liver, spleen, and kidney histology were evaluated. The total protein content of the EV fraction was quantified and the intensity and hydrodynamic diameter of EVs were measured and compared. RESULTS: BM-, AD-, and LUNG-derived EVs exhibited similar features. EVs improved survival rate and reduced static lung elastance, alveolar collapse, total number of cells, and neutrophils in alveolar septa regardless of source. CONCLUSION: In the CLP model of sepsis, BM-, AD-, and LUNG-derived EVs effectively reduce inflammation, thus improving lung histology and mechanics. EVs may hold promise for sepsis; however, further studies are required to elucidate the mechanisms of action of EVs from different sources.
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