scholarly journals Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yu Zhou ◽  
Panpan Chen ◽  
Qingnian Liu ◽  
Yingchao Wang ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dominant Negative ◽  
Beneficial Effects ◽  
Myocardial Ischemia Reperfusion

Objectives. The present study aimed to explore the major factors that account for the beneficial effects of mesenchymal stem cells (MSCs). Methods. Using isobaric tags for relative and absolute quantitation method, hepatoma-derived growth factor (HDGF) was identified as an important factor secreted by MSCs, but not by cardiac fibroblasts (CFs). The protective effects of conditioned medium (CdM) from MSCs or CFs were tested by using either H9C2 cells that were exposed by hypoxia-reoxygenation (H/R) insult or an in vivo mouse model of myocardial ischemia-reperfusion. Results. Compared to CF-CdM, MSC-CdM conferred protection against reperfusion injury. CdM obtained from MSCs that were treated with HDGF-targeted shRNA failed to offer any protection in vitro. In addition, administration of recombinant HDGF alone recapitulated the beneficial effects of MSC-CdM, which was associated with increased protein kinase C epsilon (PKCε) phosphorylation, enhanced mitochondria aldehyde dehydrogenase family 2 activity, and decreased 4-hydroxy-2-nonenal accumulation. A significant decrease in infarct size and ameliorated cardiac dysfunction was achieved by administration of HDGF in wild-type mice, which was absent in PKCε dominant negative mice, indicating the essential roles of PKCε in HDGF-mediated protection. Conclusions. HDGF secreted from MSCs plays a key role in the protection against reperfusion injury through PKCε activation.

scholarly journals Exosomes Derived from Anoxia Preconditioned Mesenchymal Stem Cells alleviate Myocardial Ischemia Reperfusion Injury by Inhibiting Pyroptosis/ Caspase-1 Induced Apoptosis in The Deficiency of Gasdermin D

2020 ◽  
Author(s):  
Chengyu Mao ◽  
Dongjiu Li ◽  
En Zhou ◽  
Erhe Gao ◽  
Tiantian Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interacting Protein ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis

Abstract BackgroundExosomes derived from adipose-derived mesenchymal stem cells can potentially protect cardiomyocytes from myocardial ischemia reperfusion injury. It's notable that exosomes derived from adipose-derived mesenchymal stem cells underwent anoxia preconditioning showed a better cardioprotective effect than that without anoxia. Here, in vitro and in vivo studies were used to investigate the cardioprotective effects against myocardial ischemia reperfusion injury of exosomes derived from adipose-derived mesenchymal stem cells with (Int-EXO) or without anoxia (NC-EXO), respectively. Methods: Adipose-derived mesenchymal stem cells and exosomes were identified by western blot, flow cytometry, transmission electron microscopy, and nanosight. An exosome tracer assay identified exosomes absorbed by cells. An in vitro model using mice cardiomyocytes for studying anoxia-reoxygenation and an in vivo mice model of MIRI were used to investigate the cardioprotective effects of NC-Exo and Int-Exo, respectively.ResultsWe discovered that treatment with NC-EXO and Int-EXO significantly reduced the infarct size and attenuated cardiomyocyte apoptosis, In addition, Int-EXO group had a less infarct size and apoptosis degree. The mechanism revealed by RNA sequencing showed that 40 miRNAs were up-regulated in Int-EXO compared to NC-EXO. 10 of these miRNAs could bind thioredoxin-interacting protein as a downstream target gene; among these, the top-discrepant miRNA224-5p was selected for further study. Dual luciferase reporter assay and rescue study verified TXNIP as a target gene for miR-224-5p. Furthermore, the cellular death signaling pathway which Int-EXO involved in mediating was in a special form of apoptosis, not pyroptosis, induced by activated thioredoxin-interacting protein-pyroptosis-caspase1 pathway in gasdermin D-deficient cells. ConclusionThe research demonstrated adipose-derived mesenchymal stem cells exosomes attenuated MIRI by inhibiting pyroptosis-induced apoptosis in cardiomyocytes which are lack of gasdermin D. The cardioprotective effect of Int-EXO was more significant than that of NC-EXO, possibly due to treated with anoxia preconditioning, adipose-derived mesenchymal stem cells product more miRNAs targeting thioredoxin-interacting protein in exosomes to alleviate pyroptosis-induced apoptosis. These findings provide new insights into the pathogenesis and methods for intervention of myocardial ischemia reperfusion injury.

scholarly journals Fate and Effect of Intravenously Infused Mesenchymal Stem Cells in a Mouse Model of Hepatic Ischemia Reperfusion Injury and Resection

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
T. C. Saat ◽  
S. van den Engel ◽  
W. Bijman-Lachger ◽  
S. S. Korevaar ◽  
M. J. Hoogduijn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Hepatocellular Injury ◽  
Hepatic Ischemia ◽  
Beneficial Effects ◽  
Hepatic Ischemia Reperfusion

Liver ischemia reperfusion injury (IRI) is inevitable during transplantation and resection and is characterized by hepatocellular injury. Therapeutic strategies to reduce IRI and accelerate regeneration could offer major benefits. Mesenchymal stem cells (MSC) are reported to have anti-inflammatory and regeneration promoting properties. We investigated the effect of MSC in a model of combined IRI and partial resection in the mouse. Hepatic IRI was induced by occlusion of 70% of the blood flow during 60 minutes, followed by 30% hepatectomy. 2 × 105MSC or PBS were infused 2 hours before or 1 hour after IRI. Six, 48, and 120 hours postoperatively mice were sacrificed. Liver damage was evaluated by liver enzymes, histology, and inflammatory markers. Regeneration was determined by liver/body weight ratio, proliferating hepatocytes, and TGF-βlevels. Fate of MSC was visualized with 3D cryoimaging. Infusion of 2 × 105MSC 2 hours before or 1 hour after IRI and resection showed no beneficial effects. Tracking revealed that MSC were trapped in the lungs and did not migrate to the site of injury and many cells had already disappeared 2 hours after infusion. Based on these findings we conclude that intravenously infused MSC disappear rapidly and were unable to induce beneficial effects in a clinically relevant model of IRI and resection.

scholarly journals Tanshinone ⅡA Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells Derived Exosomes in Myocardial Ischemia/reperfusion Injury via Up-regulating miR-223-5p

2021 ◽  
Author(s):  
Sheng Li ◽  
Lan Li ◽  
Rui Guo ◽  
Weilong Cao ◽  
Zhihao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Myocardial Ischemia ◽  
High Throughput Sequencing ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tanshinone Iia ◽  
Intramyocardial Injection ◽  
Myocardial Ischemia Reperfusion

Abstract Background: Myocardial ischemia-reperfusion (I/R) injury is a serious obstacle for patients with coronary heart disease to benefit from post-ischemic reflow. After myocardial I/R injury, CCR2+-resident macrophages are rapidly activated and participate in the subsequent inflammatory response, whereas CCR2--resident macrophages play a major role in attenuating cardiac inflammation and promoting tissue repair. Mesenchymal stem cells (MSCs) have gradually become attractive candidates that aid in understanding the pathogenesis and progression of cardiovascular diseases. The low immunogenicity and low carcinogenicity of stem cell-derived exosomes offer advantage in treating myocardial injuries. In this study, we investigated whether MSC-derived exosomes pretreated with tanshinone IIA (TSA) could exhibit stronger cardioprotective function in an I/R rat model and explored its underlying mechanism. Methods: We investigated the effect of TSA-MSCexo on myocardial I/R injury in vivo. The overexpression of CCR2 in the rat heart was used to determine the regulatory role of CCR2 in I/R injury. High-throughput sequencing of MSCexo and TSA-MSCexo to screen differential genes to explore the mechanism of TSA-MSCexo's cardioprotective effect. Results: Compared with MSCexo, an intramyocardial injection of TSA-MSCexo was found to be more effective in rats in improving cardiac function, limiting the infarct size, inhibiting CCR2 activation, reducing monocyte infiltration and promoting angiogenesis in the heart after myocardial I/R. Moreover, CCR2 had a regulatory effect on monocyte infiltration and angiogenesis after I/R. Bioinformatics analysis and miRNA sequencing of MSCexo and TSA-MSCexo revealed miR-223-5p an effective candidate mediator for TSA-MSCexo to exert its cardioprotective function and CCR2 as the downstream target. Conclusion: In summary, our findings indicated that miR-223-5p packaged in TSA-MSCexo inhibited CCR2 activation to reduce monocyte infiltration and enhanced angiogenesis to alleviate myocardial I/R injury in rats. Thus, the development of an alternative therapy of TSA combined with stem cell-derived exosomes provides an effective strategy for the clinical therapies of ischemic cardiomyopathy.

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