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Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia
by
Liu, Airan
, Hao, Qi
, Matthay, Michael A
, Hu, Shuling
, Zhuo, Hanjing
, Lee, Jae-W
, Lee, JaeHoon
, Kim, Seonguk
, Park, Jeonghyun
, Lim, Hyungsun
in
Acute Lung Injury - microbiology
/ Acute Lung Injury - pathology
/ Acute Lung Injury - physiopathology
/ Acute Lung Injury - therapy
/ Adult
/ Aged
/ Antimicrobial agents
/ ards
/ Arterial Pressure
/ Bacteria
/ Bacterial Load
/ Bone marrow
/ Cell- and Tissue-Based Therapy
/ Cell-Derived Microparticles - drug effects
/ Clinical trials
/ Critical care
/ E coli
/ Edema
/ Escherichia coli Infections - complications
/ Female
/ Humans
/ Inflammation
/ Interferon Inducers - pharmacology
/ Leukocyte Count
/ Lung Compliance
/ Lungs
/ Male
/ Mesenchymal Stem Cells - drug effects
/ MicroRNAs
/ Middle Aged
/ Mortality
/ Neutrophils
/ Organ Culture Techniques
/ Oxygen - metabolism
/ Permeability
/ Pneumonia
/ Pneumonia, Bacterial - complications
/ Poly I-C - pharmacology
/ Proteins
/ Proteins - metabolism
/ Pulmonary Alveoli - metabolism
/ Pulmonary Alveoli - microbiology
/ Pulmonary Alveoli - pathology
/ Pulmonary arteries
/ Pulmonary Artery
/ Pulmonary Edema - microbiology
/ Pulmonary Edema - therapy
/ pulmonary oedema
/ Sepsis
/ Stem cells
/ Toll-Like Receptor 3 - agonists
/ Transplants & implants
/ Tumor Necrosis Factor-alpha - metabolism
2019
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Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia
by
Liu, Airan
, Hao, Qi
, Matthay, Michael A
, Hu, Shuling
, Zhuo, Hanjing
, Lee, Jae-W
, Lee, JaeHoon
, Kim, Seonguk
, Park, Jeonghyun
, Lim, Hyungsun
in
Acute Lung Injury - microbiology
/ Acute Lung Injury - pathology
/ Acute Lung Injury - physiopathology
/ Acute Lung Injury - therapy
/ Adult
/ Aged
/ Antimicrobial agents
/ ards
/ Arterial Pressure
/ Bacteria
/ Bacterial Load
/ Bone marrow
/ Cell- and Tissue-Based Therapy
/ Cell-Derived Microparticles - drug effects
/ Clinical trials
/ Critical care
/ E coli
/ Edema
/ Escherichia coli Infections - complications
/ Female
/ Humans
/ Inflammation
/ Interferon Inducers - pharmacology
/ Leukocyte Count
/ Lung Compliance
/ Lungs
/ Male
/ Mesenchymal Stem Cells - drug effects
/ MicroRNAs
/ Middle Aged
/ Mortality
/ Neutrophils
/ Organ Culture Techniques
/ Oxygen - metabolism
/ Permeability
/ Pneumonia
/ Pneumonia, Bacterial - complications
/ Poly I-C - pharmacology
/ Proteins
/ Proteins - metabolism
/ Pulmonary Alveoli - metabolism
/ Pulmonary Alveoli - microbiology
/ Pulmonary Alveoli - pathology
/ Pulmonary arteries
/ Pulmonary Artery
/ Pulmonary Edema - microbiology
/ Pulmonary Edema - therapy
/ pulmonary oedema
/ Sepsis
/ Stem cells
/ Toll-Like Receptor 3 - agonists
/ Transplants & implants
/ Tumor Necrosis Factor-alpha - metabolism
2019
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Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia
by
Liu, Airan
, Hao, Qi
, Matthay, Michael A
, Hu, Shuling
, Zhuo, Hanjing
, Lee, Jae-W
, Lee, JaeHoon
, Kim, Seonguk
, Park, Jeonghyun
, Lim, Hyungsun
in
Acute Lung Injury - microbiology
/ Acute Lung Injury - pathology
/ Acute Lung Injury - physiopathology
/ Acute Lung Injury - therapy
/ Adult
/ Aged
/ Antimicrobial agents
/ ards
/ Arterial Pressure
/ Bacteria
/ Bacterial Load
/ Bone marrow
/ Cell- and Tissue-Based Therapy
/ Cell-Derived Microparticles - drug effects
/ Clinical trials
/ Critical care
/ E coli
/ Edema
/ Escherichia coli Infections - complications
/ Female
/ Humans
/ Inflammation
/ Interferon Inducers - pharmacology
/ Leukocyte Count
/ Lung Compliance
/ Lungs
/ Male
/ Mesenchymal Stem Cells - drug effects
/ MicroRNAs
/ Middle Aged
/ Mortality
/ Neutrophils
/ Organ Culture Techniques
/ Oxygen - metabolism
/ Permeability
/ Pneumonia
/ Pneumonia, Bacterial - complications
/ Poly I-C - pharmacology
/ Proteins
/ Proteins - metabolism
/ Pulmonary Alveoli - metabolism
/ Pulmonary Alveoli - microbiology
/ Pulmonary Alveoli - pathology
/ Pulmonary arteries
/ Pulmonary Artery
/ Pulmonary Edema - microbiology
/ Pulmonary Edema - therapy
/ pulmonary oedema
/ Sepsis
/ Stem cells
/ Toll-Like Receptor 3 - agonists
/ Transplants & implants
/ Tumor Necrosis Factor-alpha - metabolism
2019
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Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia
Journal Article
Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia
2019
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Overview
BackgroundWe previously reported that microvesicles (MVs) released by human mesenchymal stem cells (MSC) were as effective as the cells themselves in both Escherichia coli lipopolysaccharide and live bacteria-induced acute lung injury (ALI) mice models. However, it remained unclear whether the biological effect of MSC MV can be applied to human ALI.MethodsIn the current study, we tested the therapeutic effects of MSC MVs in a well-established ex vivo perfused human model of bacterial pneumonia. Using human donor lungs not used for transplantation, we instilled E. coli bacteria intrabronchially and, 1 hour later, administered MSC MVs into the perfusate as therapy.ResultsAfter 6 hours, instillation of E. coli bacteria caused influx of inflammatory cells, which resulted in significant inflammation, lung protein permeability and pulmonary oedema formation. Administration of MSC MV significantly increased alveolar fluid clearance and reduced protein permeability and numerically lowered the bacterial load in the injured alveolus. The beneficial effect on bacterial killing was more pronounced with pretreatment of MSCs with a Toll-like receptor 3 agonist, polyinosinic:polycytidylic acid (Poly (I:C)), prior to the isolation of MVs. Isolated human alveolar macrophages had increased antimicrobial activity with MSC MV treatment in vitro as well. Although oxygenation and lung compliance levels were similar between injury and treatment groups, administration of MSC MVs numerically decreased median pulmonary artery pressure at 6 hours.ConclusionsIn summary, MSC MVs increased alveolar fluid clearance and reduced lung protein permeability, and pretreatment with Poly (I:C) enhanced the antimicrobial activity of MVs in an ex vivo perfused human lung with severe bacteria pneumonia.
Publisher
BMJ Publishing Group Ltd and British Thoracic Society,BMJ Publishing Group LTD
Subject
Acute Lung Injury - microbiology
/ Acute Lung Injury - pathology
/ Acute Lung Injury - physiopathology
/ Adult
/ Aged
/ ards
/ Bacteria
/ Cell- and Tissue-Based Therapy
/ Cell-Derived Microparticles - drug effects
/ E coli
/ Edema
/ Escherichia coli Infections - complications
/ Female
/ Humans
/ Interferon Inducers - pharmacology
/ Lungs
/ Male
/ Mesenchymal Stem Cells - drug effects
/ Pneumonia, Bacterial - complications
/ Proteins
/ Pulmonary Alveoli - metabolism
/ Pulmonary Alveoli - microbiology
/ Pulmonary Alveoli - pathology
/ Pulmonary Edema - microbiology
/ Sepsis
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