Bone Marrow Mesenchymal Stem Cell-Derived Hepatocyte-Like Cell Exosomes Reduce Hepatic Ischemia/Reperfusion Injury by Enhancing Autophagy

2020 ◽  
Vol 29 (6) ◽  
pp. 372-379 ◽  
Author(s):  
Bo Yang ◽  
Wu Duan ◽  
Lai Wei ◽  
Yuanyuan Zhao ◽  
Zhenyi Han ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

scholarly journals Protective Effects of Human Liver Stem Cell-Derived Extracellular Vesicles in a Mouse Model of Hepatic Ischemia-Reperfusion Injury

2020 ◽  
Author(s):  
Alberto Calleri ◽  
Dorotea Roggio ◽  
Victor Navarro-Tableros ◽  
Nicola De Stefano ◽  
Chiara Pasquino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Reperfusion Injury ◽  
Extracellular Vesicles ◽  
Human Liver ◽  
Imaging System ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

AbstractHepatic ischemia-reperfusion injury (IRI) is observed in liver transplantation and hepato-biliary surgery and is associated with an inflammatory response. Human liver stem cell-derived extracellular vesicles (HLSC-EV) have been demonstrated to reduce liver damage in different experimental settings by accelerating regeneration and by modulating inflammation. The aim of the present study was to investigate whether HLSC-EV may protect liver from IRI in a mouse experimental model. Segmental IRI was obtained by selective clamping of intrahepatic pedicles for 90 min followed by 6 h of reperfusion. HLSC-EV were administered intravenously at the end of the ischemic period and histopathological and biochemical alterations were evaluated in comparison with controls injected with vehicle alone. Intra liver localization of labeled HLSC-EV was assessed by in in vivo Imaging System (IVIS) and the internalization into hepatocytes was confirmed by fluorescence analyses. As compared to the control group, administration of 3 × 109 particles (EV1 group) significantly reduced alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release, necrosis extension and cytokines expression (TNF-α, CCL-2 and CXCL-10). However, the administration of an increased dose of HLSC-EV (7.5 × 109 particles, EV2 group) showed no significant improvement in respect to controls at enzyme and histology levels, despite a significantly lower cytokine expression. In conclusion, this study demonstrated that 3 × 109 HLSC-EV were able to modulate hepatic IRI by preserving tissue integrity and by reducing transaminases release and inflammatory cytokines expression. By contrast, a higher dose was ineffective suggesting a restricted window of biological activity.

scholarly journals Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7

2019 ◽  
Vol 465 (1-2) ◽  
pp. 103-114 ◽  
Author(s):  
Qi Chen ◽  
Yu Liu ◽  
Xueyan Ding ◽  
Qinfeng Li ◽  
Fuyu Qiu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Myocardial Ischemia ◽  
Western Blot ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

AbstractMicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosomes carrying miR-125b on I/R rats. The myocardial I/R model in rats was constructed by ligation of the left anterior descending coronary artery (LAD). Rats were randomly divided into I/R and Sham group. Lv-cel-miR-67 (control) or Lv-miR-125b was transfected into BMSCs. Exosomes were extracted from transfected BMSCs, and separately named BMSC-Exo-67, BMSC-Exo-125b, and BMSC-Exo. MTT assay and flow cytometry were used to detect the viability and apoptosis of I/R myocardium cells, respectively. The expression of cell apoptosis proteins and the levels of inflammatory factors were examined by Western blot and ELISA assay, respectively. The target relationship between miR-125b and SIRT7 was predicted by using StarBase3.0, and was confirmed by using dual-luciferase reporter gene assay. qRT-PCR, immunohistochemistry staining, and Western blot were used to evaluate the expression of SIRT7 in myocardium tissues in I/R rats. BMSC-derived exosomes were successfully isolated and identified by TEM and positive expression of CD9 and CD63. The expression of miR-125b was down-regulated in I/R myocardium tissues and cells. BMSC-Exo-125b significantly up-regulated miR-125b in I/R myocardium cells. The intervention of BMSC-Exo-125b significantly increased the cell viability, decreased the apoptotic ratio, down-regulated Bax and caspase-3, up-regulated Bcl-2, and decreased the levels of IL-1β, IL-6, and TNF-α in I/R myocardium cells. SIRT7 was a target of miR-125b, and BMSC-Exo-125b significantly down-regulated SIRT7 in myocardium cells. In addition, the injection of BMSC-Exo-125b alleviated the pathological damages and down-regulated SIRT7 in myocardium tissues of I/R rats. BMSC-derived exosomes carrying miR-125b protected against myocardial I/R by targeting SIRT7.

scholarly journals Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats

2021 ◽  
Author(s):  
Hu Tian ◽  
Wan-song Zhang ◽  
Cheng Yang ◽  
Jun-hao Zhou ◽  
Ran-ran Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Stem Cell ◽  
Treatment Group ◽  
Mesenchymal Stem Cell ◽  
Reperfusion Injury ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Testicular Ischemia

Abstract Background: Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury.Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group.Conclusion: BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。

scholarly journals Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats

2021 ◽  
Author(s):  
Hu Tian ◽  
Wan-song Zhang ◽  
Cheng Yang ◽  
Jun-hao Zhou ◽  
Ran-ran Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Stem Cell ◽  
Treatment Group ◽  
Mesenchymal Stem Cell ◽  
Reperfusion Injury ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Testicular Ischemia

Abstract Background Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury. Methods Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group. Conclusion BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。

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