Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

Aim: We aimed to investigate the protection of exogenous miR-19a/19b with bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation on cardiac function and inhibition of fibrosis in myocardial infarction (MI). Materials & methods: BM-MSC-derived exosomes were used to deliver miR-19a/19b (exo/miR-19a/19b) to the cultured cardiac HL-1 cells, and the apoptosis of cells were evaluated. Exo/miR-19a/19b and BM-MSCs were also transplanted to an in vivo MI mouse model. The recovery of cardiac function was assessed and the level of cardiac fibrosis was determined. Results: Exo/miR-19a/19b and MSCs reduced the area of cardiac fibrosis in the heart tissue in the mouse MI model. Using BM-MSC-derived exosomes as a vehicle, miR-19a/19b significantly suppressed the apoptosis of cardiac HL-1 cells. The combination of Exo/miR-19a/19b and MSC transplantation significantly enhanced the recovery of cardiac function and reduced cardiac fibrosis in the MI model. Conclusion: Our study provides an effective regenerative intervention strategy to attenuate the damage of MI.

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

Perfusion ◽

10.1177/0267659119847442 ◽

2019 ◽

Vol 34 (8) ◽

pp. 696-704 ◽

Cited By ~ 2

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.

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Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction

Stem Cell Research ◽

10.1016/j.scr.2011.01.001 ◽

2011 ◽

Vol 6 (3) ◽

pp. 206-214 ◽

Cited By ~ 243

Author(s):

Leo Timmers ◽

Sai Kiang Lim ◽

Imo E. Hoefer ◽

Fatih Arslan ◽

Ruenn Chai Lai ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cardiac Function ◽

Conditioned Medium ◽

Human Mesenchymal Stem Cell ◽

Cell Conditioned Medium

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Multiple Intravenous Injections of Valproic Acid-Induced Mesenchymal Stem Cell from Human-Induced Pluripotent Stem Cells Improved Cardiac Function in an Acute Myocardial Infarction Rat Model

BioMed Research International ◽

10.1155/2020/2863501 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Shuyuan Guo ◽

Yusen Zhang ◽

Yanmin Zhang ◽

Fanhua Meng ◽

Minghua Li ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cardiac Function ◽

Pluripotent Stem Cells ◽

Left Ventricular ◽

Intravenous Injections ◽

Injection Control ◽

Induced Pluripotent

Mounting evidence indicates that the mesenchymal stem cell (MSC) injection is safe and efficacious for treating cardiomyopathy; however, there is limited information relating to multiple intravenous injections of human-induced pluripotent stem cell-derived mesenchymal stem cell (hiPSC-MSC) and long-term evaluation of the cardiac function. In the current study, MSC-like cells were derived from human-induced pluripotent stem cells through valproic acid (VPA) induction and continuous cell passages. The derived spindle-like cells expressed MSC-related markers, secreted angiogenic and immune-regulatory factors, and could be induced to experience chondrogenic and adipogenic differentiation. During the induction process, expression of epithelial-to-mesenchymal transition- (EMT-) related gene N-cadherin and vimentin was upregulated to a very high level, and the expression of pluripotency-related genes Sox2 and Oct4 was downregulated or remained unchanged, indicating that VPA initiated EMT by upregulating the expression of EMT promoting genes and downregulating that of pluripotency-related genes. Two and four intravenous hiPSC-MSC injections (106 cells/per injections) were provided, respectively, to model rats one week after acute myocardial infarction (AMI). Cardiac function parameters were dynamically monitored during a 12-week period. Two and four cell injections significantly the improved left ventricular ejection fraction and left ventricular fractional shortening; four-injection markedly stimulated angiogenesis reduced the scar size and cell apoptosis number in the scar area in comparison with that of the untreated control model rats. Although the difference was insignificant, the hiPSC-MSC administration delayed the increase of left ventricular end-diastolic dimension to different extents compared with that of the PBS-injection control. No perceptible immune reaction symptom or hiPSC-MSC-induced tumour formation was found over 12 weeks. Compared with the PBS-injection control, four injections produced better outcome than two injections; as a result, at least four rounds of MSC injections were suggested for AMI treatment.

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