The Mechanism of Rhein Ameliorating the Survival Rate of Transplanted Mesenchymal Stem Cells by Improving Myocardial Microenvironment in Acute Myocardial Infarction

2021 ◽  
Vol 11 (4) ◽  
pp. 684-689
Author(s):  
Xuejun Deng ◽  
Xiaojun He ◽  
Gang Huang ◽  
Dongmei Yu ◽  
Xiaozhen Lin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Survival Rate ◽  
Heart Function ◽  
Immunofluorescence Staining ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Myocardial Tissue ◽  
Tnf Α ◽  
Myocardial Fibers

Background: The paper investigated the mechanism of Rhein improving the ischemic myocardial microenvironment, promoting the survival rate of transplanted BMSCs and functional recovery of damaged myocardium by alleviating myocardial ERS-mediated hyperinflammation and apoptosis after AMI. Material and Methods: A model of myocardial infarction was established. BLI was used to detect the survival rate of transplanted stem cells at 1, 7, 14, 21 and 28 days after surgery. TUNEL staining was used to assess apoptosis. ERS-related protein CHOP immunofluorescence staining was used to assess ERS level. The expressions of ERS-related biomarkers ATF4, CHOP, GRP78 and GRP94 were detected by Western Blot. The inflammatory factors IL-6, TNF-α and IL- 10 of myocardial tissue were detected by ELISA. CD31 immunization was performed 28 days after surgery. Fluorescence staining was used to assess tissue angiogenesis. Results: Rhein combined with BMSCs could improve cardiac function, decrease apoptosis and myocardial CHOP expression. WB showed that the expressions of ATF4, CHOP, GRP78 and GRP94 in myocardial tissue of MI rats were decreased. ELISA showed that Rhein can inhibit the expressions of pro-inflammatory factors IL-6 and TNF-α, and promote anti-inflammatory factors IL-10 expression. CD31 immunofluorescence staining showed that Rhein can promote the formation of neovascularization in infarcted myocardium. Conclusion: In AMI, myocardial ERS is activated. Rhein inhibits ERS and the mediated inflammation and oxidative stress after AMI, inhibits apoptosis, improves the survival rate of transplanted BMSCs, enhances BMSCs to promote neovascularization, inhibits myocardial fibers, and improves heart function.

scholarly journals Trop2 Guarantees Cardioprotective Effects of Cortical Bone-Derived Stem Cells on Myocardial Ischemia/Reperfusion Injury

2018 ◽  
Vol 27 (8) ◽  
pp. 1256-1268 ◽  
Author(s):  
Tianyu Li ◽  
Yunshu Su ◽  
Xiongli Yu ◽  
Durgahee S.A. Mouniir ◽  
Jackson Ferdinand Masau ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Myocardial Ischemia ◽  
Cortical Bone ◽  
Heart Function ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Promising Therapeutic Approach ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Stem cell transplantation represents a promising therapeutic approach for myocardial ischemia/reperfusion (I/R) injury, where cortical bone-derived stem cells (CBSCs) stand out and hold superior cardioprotective effects on myocardial infarction than other types of stem cells. However, the molecular mechanism underlying CBSCs function on myocardial I/R injury is poorly understood. In a previous study, we reported that Trop2 (trophoblast cell-surface antigen 2) is expressed exclusively on the CBSCs membrane, and is involved in regulation of proliferation and differentiation of CBSCs. In this study, we found that the Trop2 is essential for the ameliorative effects of CBSCs on myocardial I/R-induced heart damage via promoting angiogenesis and inhibiting cardiomyocytes apoptosis in a paracrine manner. Trop2 is required for the colonization of CBSCs in recipient hearts. When Trop2 was knocked out, CBSCs largely lost their functions in lowering myocardial infarction size, improving heart function, enhancing capillary density, and suppressing myocardial cell death. Mechanistically, activating the AKT/GSK3β/β-Catenin signaling axis contributes to the essential role of Trop2 in CBSCs-rendered cardioprotective effects on myocardial I/R injury. In conclusion, maintaining the expression and/or activation of Trop2 in CBSCs might be a promising strategy for treating myocardial infarction, I/R injury, and other related heart diseases.

scholarly journals Mesenchymal stem cells with overexpression of Angiotensin-converting enzyme-2 improved the microenvironment and cardiac function in a rat model of myocardial infarction

2020 ◽  
Author(s):  
Chao Liu ◽  
Yue Fan ◽  
Hong-Yi Zhu ◽  
Lu zhou ◽  
Yu Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Angiotensin Converting Enzyme ◽  
Cardiac Function ◽  
Heart Function ◽  
Tube Formation ◽  
Border Zone ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

AbstractBackgroundAngiotensin-converting enzyme-2 (ACE2) overexpression improves left ventricular remodeling and function in diabetic cardiomyopathy; however, the effect of ACE2-overexpressed mesenchymal stem cells (MSCs) on myocardial infarction (MI) remains unexplored. This study aimed to investigate the effect of ACE2-overexpression on the function of MSCs and the therapeutic efficacy of MSCs for MI.MethodsMSCs were transfected with Ace2 gene using lentivirus, and then transplanted into the border zone of ischemic heart. The renin-angiotensin system (RAS) expression, nitric oxide synthase (NOS) expression, paracrine factors, anti-hypoxia ability, tube formation of MSCs, and heart function were determined.ResultsMSCs expressed little ACE2. ACE2-overexpression decreased the expression of AT1 and VEGF apparently, up-regulated the paracrine of HGF, and increased the synthesis of Angiotensin 1-7 in vitro. ACE2-overexpressed MSCs showed a cytoprotective effect on cardiomyocyte, and an interesting tube formation ability, decreased the heart fibrosis and infarct size, and improved the heart function.ConclusionTherapies employing MSCs with ACE2 overexpression may represent an effective treatment for improving the myocardium microenvironment and the cardiac function after MI.

scholarly journals Cardiac Regeneration After Myocardial Infarction: an Approachable Goal

2020 ◽  
Vol 22 (10) ◽  
Author(s):  
Mauro Giacca
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Adult Stem Cells ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Myocardial Tissue ◽  
Induced Pluripotent ◽  
Large Animals

Abstract Purpose of Review Until recently, cardiac regeneration after myocardial infarction has remained a holy grail in cardiology. Failure of clinical trials using adult stem cells and scepticism about the actual existence of such cells has reinforced the notion that the heart is an irreversibly post-mitotic organ. Recent evidence has drastically challenged this conclusion. Recent Findings Cardiac regeneration can successfully be obtained by at least two strategies. First, new cardiomyocytes can be generated from embryonic stem cells or induced pluripotent stem cells and administered to the heart either as cell suspensions or upon ex vivo generation of contractile myocardial tissue. Alternatively, the endogenous capacity of cardiomyocytes to proliferate can be stimulated by the delivery of individual genes or, more successfully, of selected microRNAs. Summary Recent experimental success in large animals by both strategies now fuels the notion that cardiac regeneration is indeed possible. Several technical hurdles, however, still need to be addressed and solved before broad and successful clinical application is achieved.

scholarly journals Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

2020 ◽  
Vol 21 (19) ◽  
pp. 7301 ◽  
Author(s):  
Kamila Raziyeva ◽  
Aiganym Smagulova ◽  
Yevgeniy Kim ◽  
Saltanat Smagul ◽  
Ayan Nurkesh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Heart Function ◽  
Cellular Reprogramming ◽  
Genetic Manipulations ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction. However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells. Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application. In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents. Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well.

scholarly journals Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

2020 ◽  
Vol 9 (6) ◽  
pp. 1711 ◽  
Author(s):  
Adrien A. Eshraghi ◽  
Emre Ocak ◽  
Angela Zhu ◽  
Jeenu Mittal ◽  
Camron Davies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inner Ear ◽  
Cell Damage ◽  
Tunel Staining ◽  
Tnf Α ◽  
Rat Cochlea ◽  
Necrosis Factor

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

scholarly journals Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Aiming Wu ◽  
Jianying Zhai ◽  
Dongmei Zhang ◽  
Lixia Lou ◽  
Haiyan Zhu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tunel Staining ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Myocardial Apoptosis

Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI).Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA).Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI.Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI.

scholarly journals Klotho protects chondrocyte viability via FOXO1/3 in osteoarthritis

2021 ◽  
Vol 20 (9) ◽  
pp. 1961-1968
Author(s):  
Wei Wei ◽  
Liefeng Ji ◽  
Wanli Duan ◽  
Jiang Zhu
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Protective Effect ◽  
Collagen I ◽  
Inflammatory Factors ◽  
Ros Production ◽  
Chondrocyte Viability ◽  
Tnf Α ◽  
Collagen Ii

Purpose: To investigate the effect of Klotho and FOXO1/3 on the CH viability in OA.Methods: The survival rate of CHs, Klotho and FOXO1/3 protein expression, and ROS production were measured in the OA cartilages of different degenerative phases. H2O2 was also used to injure CHs, and the cell viability, Klotho and FOXO1/3 expressions, as well as ROS levels were investigated to clarify the effect of exogenic Klotho on the injured CHs. Additionally, in order to verify the role of FOXO1/3 in Klotho-treated CHs, SOD2, GPX1, inflammatory factors, collagen I/II, SOX9, and Runx-2 levels were analyzed by silencing FOXO1 and FOXO3 expression via siRNA transfection.Results: Klotho and FOXO1/3 expressions significantly decreased, and ROS production increased in severely human OA cartilage (p <0.05). Besides, H2O2 affected CHs viability with the suppression of Klotho and FOXO1/3 expression but ROS production was elevated. Exogenic Klotho application partly reversed the injury caused by H2O2. Furthermore, Klotho treatment of the injured CHs contributed to SOD2 and GPX1 expressions, and suppressed IL-1β, IL-6, TNF-α and MMP-13 production, resulting in  the upregulation of collagen II and SOX9 as well as downregulation of collagen I and Runx-2. However, the protective effect of Klotho was weakened by FOXO1 and FOXO3 gene silencing.Conclusion: Klotho protects CHs viability by suppressing oxidative stress and inflammation, which is associated with the mediation of FOXO1 and FOXO3. These findings provide new insights into the treatment of OA.

scholarly journals Ticagrelor alleviates sepsis-induced myocardial injury via an adenosine-dependent pathway in a mouse sepsis model

2020 ◽  
Vol 43 (4) ◽  
pp. E44-55
Author(s):  
Shengxing Tang ◽  
Cong Fu ◽  
Qiancheng Xu ◽  
Wenjun Guo ◽  
Yuhan Cao
Keyword(s):  
Western Blot ◽  
Protective Effect ◽  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Myocardial Injury ◽  
Cardiomyocyte Apoptosis ◽  
Tunel Staining ◽  
Myocardial Tissue ◽  
Adenosine Receptor Antagonist ◽  
Tnf Α

Purpose: The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury. Methods: The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue. Results: The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR. Conclusion: The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.

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