scholarly journals PO-301 Study on the effects of bone marrow-derived stem cells were used in chronic hyperactivity rats to cardiac injury treatment

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Lei Xu ◽  
YiBo Niu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Test Data ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Training Group ◽  
Significant Difference ◽  
General Training

Objective  overload and long-term overtraining can cause hypoxic and hypoxic damage to the myocardial structure of the body. In recent years, studies have shown that the stem cells promote angiogenesis in vivo, resistance to apoptosis, myocardial stem cell mobilization, and promote its proliferation in paracrine effect, such as vascular distribution. By animal experiments, this study explore MSCMs role in the improvement of heart function and its molecular mechanism to sports injury prevention and postoperative rehabilitation is of great significance of the heart, heart research provides the basis for the motion at the same time support. Methods Wistar rat model of excessive swimming training. Grouping: rats were randomly divided into 4 groups (n=10), quiet feeding group (Q), general training group (ET), over-training group (OT), and MSCMs transplant-over-training group (MOT). Source and preparation of stem cells: the rat autologous bone marrow was extracted 1 day before surgery, and the bone marrow mononuclear cells were isolated by Ficoll density gradient centrifugation. Methods of stem cell transplantation: perfusion via coronary artery in MOT group rats; Test indicators and methods: cardiac tissue was taken after the end of 1d training (group Q, ET and OT), MEF2A factor was tested by rcal-time, gata-4 expression was tested by Western blot, and LVEF value was observed by cardiac color doppler ultrasound (before, after 1w, after 2w and after 3w, respectively). Results MEF2A factor, gata-4 expression and LVEF value of the three groups of samples were detected: (1) compared with MEF2A factor in general training group (ET) and quiet group (Q), gata-4 expression was slightly improved, but there was no significant difference (P>0.05). After 3w, the increase of LVEF value presented significant differences (Pwhile 1w and 2w showed no significant differences compared with the quiet group. (2) comparison between the over-training group (OT) and the quiet group (Q) showed significant differences in MEF2A factor, gata-4 expression, and LVEF decreased value (P0.05) between the two groups after 2w and the quiet group (Q). Cardiac tissue was taken after 2w to observe the expression of MEF2A, and gata-4 was compared with the silent group (Q) without significant difference (P>0.05). Conclusions (1) based on the test data of general training group (ET), reasonable and scientific aerobic exercise can effectively enhance the cardiac function and improve the cardiac activity ability. (2) according to the test data of over-training group (OT), overloading and long-term over-training can lead to hypoxia of heart function and decrease of vitality, resulting in hypoxia and ischemia of the motor heart and damage of cardiac function. (3) according to the observation and test data of the MSCMs transplant-over-training group (MOT), MSCMs transplantation can effectively improve the cardiac function of sports injuries, enhance the cardiac vitality, and repair damaged cells and tissues to a certain extent. It can effectively prevent and treat heart injury caused by overtraining. At the same time, it provides animal experimental research support for the research of sports heart in sports medicine.

scholarly journals Identification of RyR2-PBmice and the effects of transposon insertional mutagenesis of the RyR2 gene on cardiac function in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6942
Author(s):  
Qianqian Wang ◽  
Chao Wang ◽  
Bo Wang ◽  
Qirui Shen ◽  
Leilei Qiu ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Insertional Mutagenesis ◽  
Cardiac Tissue ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Heart Diseases ◽  
Mrna Level ◽  
Significant Difference ◽  
Cardiac Function Tests ◽  
And Function

Ryanodine receptor 2 (RyR2) plays an important role in maintaining the normal heart function, and mutantions can lead to arrhythmia, heart failure and other heart diseases. In this study, we successfully identified a piggyBac translocated RyR2 gene heterozygous mouse model (RyR2-PBmice) by tracking red fluorescent protein (RFP) and genotyping PCR. Cardiac function tests showed that there was no significant difference between the RyR2-PBmice and corresponding wild-type mice (WTmice), regardless of whether they were in the basal state or injected with epinephrine and caffeine. However, the sarcoplasmic reticulum Ca2+ content was significantly reduced in the cardiomyocytes of RyR2-PBmice as assessed by measuring caffeine-induced [Ca2+]i transients; the cardiac muscle tissue of RyR2-PBmice displayed significant mitochondrial swelling and focal dissolution of mitochondrial cristae, and the tissue ATP content in the RyR2-PBmice heart was significantly reduced. To further analyze the molecular mechanism behind these changes, we tested the expression levels of related proteins using RT-PCR and Western blot analyses. The mRNA level of RyR2 in RyR2-PBmice cardiac tissue decreased significantly compared with the WTmice, and the protein expression associated with the respiratory chain was also downregulated. These results suggested that the piggyBac transposon inserted into the RyR2 gene substantively affected the structure and function of mitochondria in the mouse cardiomyocytes, leading to disorders of energy metabolism.

Bone marrow mesenchymal stem cells overexpressing GATA-4 improve cardiac function following myocardial infarction

Perfusion ◽  
2019 ◽  
Vol 34 (8) ◽  
pp. 696-704 ◽  
Author(s):  
Ji-Gang He ◽  
Hong-Rong Li ◽  
Bei-Bei Li ◽  
Qiao-Li Xie ◽  
Dan Yan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cardiac Function ◽  
Cardiac Tissue ◽  
Cell Group ◽  
Marrow Mesenchymal Stem Cells

Introduction: The present study aimed to examine whether GATA-4 overexpressing bone marrow mesenchymal stem cells can improve cardiac function in a murine myocardial infarction model compared with bone marrow mesenchymal stem cells alone. Methods: A lentiviral-based transgenic system was used to generate bone mesenchymal stem cells which stably expressed GATA-4 (GATA-4-bone marrow mesenchymal stem cells). Apoptosis and the myogenic phenotype of the bone marrow mesenchymal stem cells were measured using Western blot and immunofluorescence assays co-cultured with cardiomyocytes. Cardiac function, bone marrow mesenchymal stem cell homing, cardiac cell apoptosis, and vessel number following transplantation were assessed, as well as the expression of c-Kit. Results: In GATA-4-bone marrow mesenchymal stem cells-cardiomyocyte co-cultures, expression of myocardial-specific antigens, cTnT, connexin-43, desmin, and α-actin was increased compared with bone marrow mesenchymal stem cells alone. Caspase 8 and cytochrome C expression was lower, and the apoptotic rate was significantly lower in GATA-4 bone marrow mesenchymal stem cells. Cardiac function following myocardial infarction was also increased in the GATA-4 bone marrow mesenchymal stem cell group as demonstrated by enhanced ejection fraction and left ventricular fractional shortening. Analysis of the cardiac tissue revealed that the GATA-4 bone marrow mesenchymal stem cell group had a greater number of DiR-positive cells suggestive of increased homing and/or survival. Transplantation with GATA-4-bone marrow mesenchymal stem cells significantly increased the number of blood vessels, decreased the proportion of apoptotic cells, and increased the mean number of cardiac c-kit-positive cells. Conclusion: GATA-4 overexpression in bone marrow mesenchymal stem cells exerts anti-apoptotic effects by targeting cytochrome C and Fas pathways, promotes the aggregation of bone marrow mesenchymal stem cells in cardiac tissue, facilitates angiogenesis, and effectively mobilizes c-kit-positive cells following myocardial infarction, leading to the improvement of cardiac function after MI.

Effect of Bone Marrow Mesenchymal Stem Cells (BMSCs) on Cardiac Function and Ventricular Remodeling in Diabetic Rat Models Through Inhibiting MicroRNA (miR)-34a

2021 ◽  
Vol 11 (8) ◽  
pp. 1490-1496
Author(s):  
Xiangzhen Qu ◽  
Shanyong Zhu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Negative Relationship ◽  
Left Ventricular ◽  
Ventricular Wall ◽  
Marrow Mesenchymal Stem Cells

Diabetes mellitus (DM) is harmful to heart tissue. We transplanted bone marrow mesenchymal stem cells (BMSCs) in this study to improve the function of diabetic heart. 45 rats were divided into healthy group, DM group (treated with high-fat diet), and BMSCs group (BMSCs transplantation into the ventricular wall) followed by analysis of miR-34a and aldehyde dehydrogenase 2 (ALDH2) levels, heart function, and ventricular remodeling in the three groups of rats. BMSCs were successfully cultured with high purity, and the myocardium in the BMSCs group was successfully labeled by DAPI. The left ventricular hypertrophy index and myocardial tissue CVF of rats with DM increased significantly, suggesting that ventricular remodeling in DM rats was stimulated. However, when BMSCs were transplanted to the ventricular wall, although the ventricular remodeling was not completely avoided, apoptosis of BMSCs group was significantly reduced. MiR-34a relative level in BMSCs group was obviously elevated, whereas ALDH2 level showed opposite trend with a negative relationship. MiR-34a can effectively bind to the 3′-UTR of ALDH2 mRNA, indicating that it can directly regulate gene expression. BMSCs can promote the synthesis of ALDH2 by inhibiting the expression of miR-34a, and improve the cardiac function and ventricular remodeling of diabetic rats.

Intramyocardial Injection of CD133+ Bone Marrow-Derived Stem Cells Improves Cardiac Function Long-Term in the Majority of Selected Patients with End-Stage Ischemic Heart Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5480-5480
Author(s):  
Marcus A. Stockschlaeder ◽  
Ali Ghodsizad ◽  
Volker Stoldt ◽  
Ludger Poll ◽  
Ruediger E. Scharf ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Heart Disease ◽  
Cardiac Function ◽  
Ischemic Heart Disease ◽  
Heart Function ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Intramyocardial Injection ◽  
End Stage

Abstract To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in 10 patients with end-stage ischemic heart disease. Approx. 60 – 380 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device CliniMACS. By using the Duesseldorf protocol, the intraoperative isolation of CD133+-stem cells (1.9−10.0 x 106 cells; purity up to 97%) was achieved in less than 3 hours. Following isolation, autologous CD133+-stem cells were injected in a predefined pattern into the myocardium. Cardiac function was assessed by cardiac MRI and echocardiography three, six, and nine months postoperatively. A significant improvement of cardiac function could be documented in 7 out of 10 patients: ejection fraction (EF) before treatment: 10–22% - after 3 months: 18–30% - after 6 months: 19–30%, after 9 months: 21–31%; left ventricular enddiastolic volume (LVEDV) before treatment: 210 ± 123 ml, after 3 months: 169 ± 80 ml, after 6 months: 162 ± 82 ml, after 9 months: 175 ± 70 ml; left ventricular enddiastolic diameter (LVEDD) before treatment: 79.2 ± 7 mm, after 3 months: 57.4 ± 3 mm, after 6 months: 59.4 ± 4 mm, after 9 months: 56.2 ± 5 mm, respectively. In two patients cardiac function improved only temporarily over the first three months, 1 patient died one month after surgery due to a non-cardiac cause. In conclusion, the sole intramyocardial injection of autologous CD133+-cells proved to be safe and led to a significant gain in heart function in 7 of 10 patients, thereby avoiding or postponing (“bridging”) alternative therapies such as heart transplantaton. The benefial effects of intramyocardially injected bone marrow-derived stem cells might be explained by direcct cellular effects including neovascularization and indirect effects including the formation of growth factors promoting tissue repair.

scholarly journals Exposure to Low-Dose 56Fe-Ion Radiation Induces Long-Term Epigenetic Alterations in Mouse Bone Marrow Hematopoietic Progenitor and Stem Cells

2014 ◽  
Vol 182 (1) ◽  
pp. 92 ◽  
Author(s):  
Isabelle R. Miousse ◽  
Lijian Shao ◽  
Jianhui Chang ◽  
Wei Feng ◽  
Yingying Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Low Dose ◽  
Mouse Bone Marrow ◽  
Epigenetic Alterations ◽  
Hematopoietic Progenitor

Evaluation of Canine Bone Marrow-derived Mesenchymal Stem Cells After Long-term Cryopreservation

2013 ◽  
Vol 30 (12) ◽  
pp. 1032-1037 ◽  
Author(s):  
Xiaofeng Zhu ◽  
Fang Yuan ◽  
Houxuan Li ◽  
Yuqian Zheng ◽  
Yin Xiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells

Abstract 4296: Allogeneic Bone Marrow Mesenchymal Cells Improved Heart Function but Were Rejected after Myogenic Differentiation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xi-Ping Huang ◽  
Zhuo Sun ◽  
Yasuo Miyagi ◽  
Shafie Fazel ◽  
Richard D Weisel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cardiac Function ◽  
Cell Survival ◽  
Myogenic Differentiation ◽  
Heart Function ◽  
Allogeneic Bone Marrow ◽  
Male Rats ◽  
Functional Improvement ◽  
Allogeneic Bone ◽  
Rt Pcr

Rationale: Allogeneic bone marrow mesenchymal stem cells (MSC) are currently undergoing clinical trials to test their potential to repair the heart after a myocardial infarction (MI). MSCs can improve function, but neither the host immune responses nor the fate of these cells has been extensively investigated. This study compared the outcomes of allogeneic and syngeneic MSC transplantation after an MI. Methods: Female Lewis rat underwent coronary ligation. Three weeks later, allogeneic or syngeneic MSCs (3×10 6 /rat) from male rats (Wister or Lewis, respectively) were implanted into the infracted region. We evaluated implanted cell survival (real-time PCR to quantify Y-chromosomes), cytokines (RT-PCR) and infiltrating cells (immunostaining) in the heart, and allogeneic antibodies in the blood. Cardiac function was assessed by echocardiography and pressure-volume catheters. Immune antigen expression (RT-PCR, immunostaining and flow cytometry) was characterized in the MSCs before and after myogenic differentiation. Results: At 1 week post implantation, cell survival was similar in the allogeneic and syngeneic groups. Gene expression of 11 cytokines and T-cell infiltration into the cell-implanted region were also similar, but more B-cells were observed in the allogeneic group (p<0.05 vs. syngeneic group). Allo-antibodies (IgG1) against Wistar MSCs were detected in the peripheral blood of animals that received allogeneic cells. At 5 weeks after delivery, implanted MSCs were detected only in the syngeneic group. Cardiac function was equally restored in both cell groups (ejection fraction: allogeneic=30.4±1.8%; syngeneic=29.5±2.8%; p<0.05 vs. media controls; control=24.8±3.2%); these data were supported by the pressure-volume analysis. Myogenic differentiation (expression of Nkx2.5, MyoD, MHCβ), CD86 expression and MHC class II molecules were observed in the MSCs after prolonged culture, which could explain why the cells were rejected. Conclusions: Allogeneic BMSC transplantation produced a robust cardiac functional improvement, but following myogenic differentiation the cells were no longer immunoprivileged. Rejection of the allogeneic cells could limit their long term benefit on cardiac remodeling after an MI.

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.

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