Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Lung Injury in Rat Model of Bronchopulmonary Dysplasia by Affecting Cell Survival and Angiogenesis

2020 ◽  
Vol 29 (23) ◽  
pp. 1520-1532
Author(s):  
Jingyi You ◽  
Ou Zhou ◽  
Jiang Liu ◽  
Wenjing Zou ◽  
Linghuan Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Lung Injury ◽  
Cell Survival ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Bronchopulmonary Dysplasia ◽  
Rat Model ◽  
Human Umbilical Cord

scholarly journals Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Airway Inflammation in a Rat Model of chronic obstructive pulmonary disease (COPD)

2020 ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Norashikin Zakaria ◽  
Darius Widera ◽  
Jonathan Sheard ◽  
Mitsuru Morimoto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Pulmonary Disease ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Chronic Obstructive ◽  
Human Umbilical Cord ◽  
Obstructive Pulmonary Disease

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.Methods: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSCs) derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSCs-derived EVs. Lung tissue was subjected to histological analysis using hematoxylin and eosin staining, alcian blue-periodic acid Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t-test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median±standard deviation (SD).Results: Both, transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, as well as a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions: In conclusion, we show that hUC-MSCs-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free based therapy for the treatment of COPD.

scholarly journals Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD)

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Norashikin Zakaria ◽  
Darius Widera ◽  
Jonathan Sheard ◽  
Mitsuru Morimoto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Pulmonary Disease ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Chronic Obstructive ◽  
Human Umbilical Cord ◽  
Obstructive Pulmonary Disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Airway Inflammation in a Rat Model of chronic obstructive pulmonary disease (COPD)

2020 ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Norashikin Zakaria ◽  
Darius Widera ◽  
Jonathan Sheard ◽  
Mitsuru Morimoto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Pulmonary Disease ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Chronic Obstructive ◽  
Human Umbilical Cord ◽  
Obstructive Pulmonary Disease

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSCs) derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSCs-derived EVs. Lung tissue was subjected to histological analysis using hematoxylin and eosin staining, alcian blue-periodic acid Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t-test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median±standard deviation (SD). Results: Both, transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, as well as a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions: In conclusion, we show that hUC-MSCs-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free based therapy for the treatment of COPD.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cell-derived Extracellular Vesicles Ameliorate Airway Inflammation in a Rat Model of Chronic Obstructive Pulmonary Disease (COPD)

2020 ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Norashikin Zakaria ◽  
Darius Widera ◽  
Jonathan Sheard ◽  
Mitsuru Morimoto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Pulmonary Disease ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Chronic Obstructive ◽  
Human Umbilical Cord ◽  
Obstructive Pulmonary Disease

Abstract Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. However, stem cell-based therapies are cumbersome and often associated with high costs. Extracellular vesicles (EV) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EV possess a therapeutic potential which is comparable to the cells of their origin. In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC) derived EV in a rat model of COPD. EV were isolated from hUC-MSC and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague Dawley rats were exposed to cigarette smoke for up to 12 weeks followed by transplantation of hUC-MSC or application of hUC-MSC-derived EV. Lung tissue was subjected to histological analysis using hematoxylin and eosin staining, alcian blue-periodic acid Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Both, transplantation of hUC-MSC and application of EV resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, as well as a decreased number of goblet cells. Moreover, hUC-MSC and EV ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSC and EV significantly regulate multiple pathways known to be associated with COPD. In conclusion, we show that hUC-MSC-derived EV effectively ameliorate by COPD-induced inflammation. Thus, EV could serve as a new cell-free based therapy for the treatment of COPD.

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