The Experts below are selected from a list of 4362 Experts worldwide ranked by ideXlab platform
Michael A Matthay - One of the best experts on this subject based on the ideXlab platform.
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Xiaomei Feng, Jason Abbott, Xiaohui Fang, Antoine Monsel, Jieming Qu, Michael A MatthayAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus. Stem Cells 2014;32:116–125
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Yinggang Zhu, Michael A Matthay, Xiaomei Feng, Jason Abbott, Xiaohui Fang, Qi Hao, Antoine Monsel, Jae W LeeAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.
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intrapulmonary delivery of bone marrow derived mesenchymal stem cells improves survival and attenuates Endotoxin induced acute lung injury in mice
Journal of Immunology, 2007Co-Authors: Naveen Gupta, Vladimir B. Serikov, Jaewoo Lee, B V Popov, Michael A MatthayAbstract:Recent in vivo and in vitro work suggests that mesenchymal stem cells (MSC) have anti-inflammatory properties. In this study, we tested the effect of administering MSC directly into the airspaces of the lung 4 h after the intrapulmonary administration of Escherichia Coli Endotoxin (5 mg/kg). MSC increased survival compared with PBS-treated control mice at 48 h (80 vs 42%; p < 0.01). There was also a significant decrease in excess lung water, a measure of pulmonary edema (145 ± 50 vs 87 ± 20 μl; p < 0.01), and bronchoalveolar lavage protein, a measure of endothelial and alveolar epithelial permeability (3.1 ± 0.4 vs 2.2 ± 0.8 mg/ml; p < 0.01), in the MSC-treated mice. These protective effects were not replicated by the use of further controls including fibroblasts and apoptotic MSC. The beneficial effect of MSC was independent of the ability of the cells to engraft in the lung and was not related to clearance of the Endotoxin by the MSC. MSC administration mediated a down-regulation of proinflammatory responses to Endotoxin (reducing TNF-α and MIP-2 in the bronchoalveolar lavage and plasma) while increasing the anti-inflammatory cytokine IL-10. In vitro coculture studies of MSC with alveolar macrophages provided evidence that the anti-inflammatory effect was paracrine and was not cell contact dependent. In conclusion, treatment with intrapulmonary MSC markedly decreases the severity of Endotoxin-induced acute lung injury and improves survival in mice.
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resistance of the alveolar epithelium to injury from septic shock in sheep
American Journal of Respiratory and Critical Care Medicine, 1995Co-Authors: Jean-françois Pittet, Vladimir B. Serikov, Jeanine P Wienerkronish, Michael A MatthayAbstract:Experimentally, the intravenous administration of a bolus dose of Escherichia Coli Endotoxin in sheep or a bolus dose of live Pseudomonas aeruginosa in rats is insufficient to cause injury to the alveolar epithelial barrier. Therefore, the first objective of these studies was to maximize the injury caused by live bacteria to the lung by administering a large dose of live P. aeruginosa into the lung perfusate of goat lungs in situ. P. aeruginosa (2.4 × 1010 colony-forming units [cfu]) and [131I]albumin (vascular protein tracer) were added to the lung perfusate. Even though the bacterial inoculum remained very high in this isolated perfused lung system, there was no change in the permeability to protein or clearance of fluid across the alveolar epithelium, although there was an increase in lung endothelial protein permeability. Therefore, since systemic factors have been implicated in the severity and pathogenesis of septic lung injury, the second objective was to administer a continuous intravenous infusio...
Antoine Monsel - One of the best experts on this subject based on the ideXlab platform.
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study of bone marrow and embryonic stem cell derived human mesenchymal stem cells for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells Translational Medicine, 2015Co-Authors: Qi Hao, Yinggang Zhu, Antoine Monsel, Stephane Gennai, Travis Lee, Jaewoo LeeAbstract:Mesenchymal stem cells (MSCs) can be derived from multiple tissue sources. However, the optimal source of MSCs for cell-based therapy for acute lung injury (ALI) is unclear. In the present experiments, we studied bone marrow (BM)-derived and embryonic stem cell-derived human MSC (ES-MSCs) as a therapeutic agent in Escherichia Coli Endotoxin-induced ALI in mice. We hypothesized that ES-MSCs would be more potent than BM-MSCs owing to its more primitive source of origin. ALI was induced by the intratracheal instillation of Endotoxin at 4 mg/kg into 10–12-week-old C57BL/6 mice with or without BM-MSCs, ES-MSCs, or normal human lung fibroblasts as a cellular control. Compared with the Endotoxin-injured mice at 48 hours, the administration of ES-MSCs provided results similar to those of BM-MSCs, significantly reducing the influx of white blood cells and neutrophils and decreasing the secretion of the inflammatory cytokines, macrophage inflammatory protein-2 and tumor necrosis factor-α, in the injured alveolus. BM-MSCs also reduced extravascular lung water, a measure of pulmonary edema, by 60% and the total protein levels, a measure of lung permeability, by 66%. However, surprisingly, ES-MSCs did not have these protective effects, which was partially explained by the increased secretion of matrix metallopeptidase 9 by ES-MSCs, an enzyme known to increase lung protein permeability. In conclusion, both BM-MSCs and ES-MSCs markedly decreased Endotoxin-induced inflammation. However, ES-MSCs did not show any beneficial effect on reducing pulmonary edema and lung protein permeability compared with BM-MSCs, suggesting that not all MSCs behave in a similar fashion. Our results highlight the need perhaps for a disease-specific potency assay for MSCs.
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Yinggang Zhu, Michael A Matthay, Xiaomei Feng, Jason Abbott, Xiaohui Fang, Qi Hao, Antoine Monsel, Jae W LeeAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Xiaomei Feng, Jason Abbott, Xiaohui Fang, Antoine Monsel, Jieming Qu, Michael A MatthayAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus. Stem Cells 2014;32:116–125
Jaewoo Lee - One of the best experts on this subject based on the ideXlab platform.
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study of bone marrow and embryonic stem cell derived human mesenchymal stem cells for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells Translational Medicine, 2015Co-Authors: Qi Hao, Yinggang Zhu, Antoine Monsel, Stephane Gennai, Travis Lee, Jaewoo LeeAbstract:Mesenchymal stem cells (MSCs) can be derived from multiple tissue sources. However, the optimal source of MSCs for cell-based therapy for acute lung injury (ALI) is unclear. In the present experiments, we studied bone marrow (BM)-derived and embryonic stem cell-derived human MSC (ES-MSCs) as a therapeutic agent in Escherichia Coli Endotoxin-induced ALI in mice. We hypothesized that ES-MSCs would be more potent than BM-MSCs owing to its more primitive source of origin. ALI was induced by the intratracheal instillation of Endotoxin at 4 mg/kg into 10–12-week-old C57BL/6 mice with or without BM-MSCs, ES-MSCs, or normal human lung fibroblasts as a cellular control. Compared with the Endotoxin-injured mice at 48 hours, the administration of ES-MSCs provided results similar to those of BM-MSCs, significantly reducing the influx of white blood cells and neutrophils and decreasing the secretion of the inflammatory cytokines, macrophage inflammatory protein-2 and tumor necrosis factor-α, in the injured alveolus. BM-MSCs also reduced extravascular lung water, a measure of pulmonary edema, by 60% and the total protein levels, a measure of lung permeability, by 66%. However, surprisingly, ES-MSCs did not have these protective effects, which was partially explained by the increased secretion of matrix metallopeptidase 9 by ES-MSCs, an enzyme known to increase lung protein permeability. In conclusion, both BM-MSCs and ES-MSCs markedly decreased Endotoxin-induced inflammation. However, ES-MSCs did not show any beneficial effect on reducing pulmonary edema and lung protein permeability compared with BM-MSCs, suggesting that not all MSCs behave in a similar fashion. Our results highlight the need perhaps for a disease-specific potency assay for MSCs.
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intrapulmonary delivery of bone marrow derived mesenchymal stem cells improves survival and attenuates Endotoxin induced acute lung injury in mice
Journal of Immunology, 2007Co-Authors: Naveen Gupta, Vladimir B. Serikov, Jaewoo Lee, B V Popov, Michael A MatthayAbstract:Recent in vivo and in vitro work suggests that mesenchymal stem cells (MSC) have anti-inflammatory properties. In this study, we tested the effect of administering MSC directly into the airspaces of the lung 4 h after the intrapulmonary administration of Escherichia Coli Endotoxin (5 mg/kg). MSC increased survival compared with PBS-treated control mice at 48 h (80 vs 42%; p < 0.01). There was also a significant decrease in excess lung water, a measure of pulmonary edema (145 ± 50 vs 87 ± 20 μl; p < 0.01), and bronchoalveolar lavage protein, a measure of endothelial and alveolar epithelial permeability (3.1 ± 0.4 vs 2.2 ± 0.8 mg/ml; p < 0.01), in the MSC-treated mice. These protective effects were not replicated by the use of further controls including fibroblasts and apoptotic MSC. The beneficial effect of MSC was independent of the ability of the cells to engraft in the lung and was not related to clearance of the Endotoxin by the MSC. MSC administration mediated a down-regulation of proinflammatory responses to Endotoxin (reducing TNF-α and MIP-2 in the bronchoalveolar lavage and plasma) while increasing the anti-inflammatory cytokine IL-10. In vitro coculture studies of MSC with alveolar macrophages provided evidence that the anti-inflammatory effect was paracrine and was not cell contact dependent. In conclusion, treatment with intrapulmonary MSC markedly decreases the severity of Endotoxin-induced acute lung injury and improves survival in mice.
Yinggang Zhu - One of the best experts on this subject based on the ideXlab platform.
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study of bone marrow and embryonic stem cell derived human mesenchymal stem cells for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells Translational Medicine, 2015Co-Authors: Qi Hao, Yinggang Zhu, Antoine Monsel, Stephane Gennai, Travis Lee, Jaewoo LeeAbstract:Mesenchymal stem cells (MSCs) can be derived from multiple tissue sources. However, the optimal source of MSCs for cell-based therapy for acute lung injury (ALI) is unclear. In the present experiments, we studied bone marrow (BM)-derived and embryonic stem cell-derived human MSC (ES-MSCs) as a therapeutic agent in Escherichia Coli Endotoxin-induced ALI in mice. We hypothesized that ES-MSCs would be more potent than BM-MSCs owing to its more primitive source of origin. ALI was induced by the intratracheal instillation of Endotoxin at 4 mg/kg into 10–12-week-old C57BL/6 mice with or without BM-MSCs, ES-MSCs, or normal human lung fibroblasts as a cellular control. Compared with the Endotoxin-injured mice at 48 hours, the administration of ES-MSCs provided results similar to those of BM-MSCs, significantly reducing the influx of white blood cells and neutrophils and decreasing the secretion of the inflammatory cytokines, macrophage inflammatory protein-2 and tumor necrosis factor-α, in the injured alveolus. BM-MSCs also reduced extravascular lung water, a measure of pulmonary edema, by 60% and the total protein levels, a measure of lung permeability, by 66%. However, surprisingly, ES-MSCs did not have these protective effects, which was partially explained by the increased secretion of matrix metallopeptidase 9 by ES-MSCs, an enzyme known to increase lung protein permeability. In conclusion, both BM-MSCs and ES-MSCs markedly decreased Endotoxin-induced inflammation. However, ES-MSCs did not show any beneficial effect on reducing pulmonary edema and lung protein permeability compared with BM-MSCs, suggesting that not all MSCs behave in a similar fashion. Our results highlight the need perhaps for a disease-specific potency assay for MSCs.
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Yinggang Zhu, Michael A Matthay, Xiaomei Feng, Jason Abbott, Xiaohui Fang, Qi Hao, Antoine Monsel, Jae W LeeAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.
Xiaomei Feng - One of the best experts on this subject based on the ideXlab platform.
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Yinggang Zhu, Michael A Matthay, Xiaomei Feng, Jason Abbott, Xiaohui Fang, Qi Hao, Antoine Monsel, Jae W LeeAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.
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human mesenchymal stem cell microvesicles for treatment of Escherichia Coli Endotoxin induced acute lung injury in mice
Stem Cells, 2014Co-Authors: Xiaomei Feng, Jason Abbott, Xiaohui Fang, Antoine Monsel, Jieming Qu, Michael A MatthayAbstract:We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia Coli Endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. Coli Endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to Endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. Coli Endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus. Stem Cells 2014;32:116–125