scholarly journals Application and Progress of Combined Mesenchymal Stem Cell Transplantation in the Treatment of Ischemic Cardiomyopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ping Hua ◽  
Jian-Yang Liu ◽  
Jun Tao ◽  
Song-Ran Yang
Keyword(s):  
Myocardial Infarction ◽  
Tissue Engineering ◽  
Stem Cell ◽  
Treatment Outcome ◽  
Survival Rate ◽  
Mesenchymal Stem Cell ◽  
Ischemic Cardiomyopathy ◽  
Mesenchymal Stem Cell Transplantation ◽  
Hypoxia Preconditioning ◽  
Impact On Treatment

Treatment of ischemic cardiomyopathy caused by myocardial infarction (MI) using mesenchymal stem cell (MSC) transplantation is a widely researched field, with promising clinical application. However, the low survival rate of transplanted cells has a severe impact on treatment outcome. Currently, research is focused on investigating the strategy of combining genetic engineering, tissue engineering materials, and drug/hypoxia preconditioning to improve ischemic cardiomyopathy treatment outcome using MSC transplantation treatment (MSCTT). This review discusses the application and progress of these techniques.

scholarly journals Mitochondrial Transfer through Pericardium Contributes to Functional Recovery in Ischemic Cardiomyopathy

2020 ◽  
Author(s):  
Daisuke MORI ◽  
Shigeru MIYAGAWA ◽  
Takuji KAWAMURA ◽  
Daisuke YOSHIOKA ◽  
Hiroki HATA ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Functional Recovery ◽  
Ischemic Cardiomyopathy ◽  
Rat Cardiomyocytes ◽  
Mesenchymal Stem Cell Transplantation ◽  
Mitochondrial Transfer

Abstract Although mesenchymal stem cell transplantation has been efficacious in the treatment of ischemic cardiomyopathy, the underlying mechanisms remain unclear. Herein, we investigated whether mitochondrial transfer could explain the success of cell therapy in ischemic cardiomyopathy. Mitochondrial transfer was examined in co-cultures of human adipose-derived mesenchymal stem cells and rat cardiomyocytes under hypoxic conditions. Functional recovery was monitored in a rat model of myocardial infarction following human adipose-derived mesenchymal stem cell transplantation. In vitro, we observed mitochondrial transfer, which required formation of cell-to-cell contacts and synergistically enhanced energy metabolism. Rat cexhibited mitochondrial transfer three days following human adipose-derived mesenchymal stem cell transplantation to the ischemic heart surface post myocardial infarction. We detected donor mitochondrial DNA in the recipient myocardium concomitant with a significant improvement in cardiac function. In conclusion, mitochondrial transfer is vital for successful cell transplantation therapies and promotes improved treatment outcomes in ischemic cardiomyopathy.

Abstract 17087: Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy Delivered in a Hydrogel Preserves Hemodynamic Function Following Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mark R Helmers ◽  
Jakub Jarmula ◽  
Samuel Kim ◽  
Alexis Schiazza ◽  
Peter Altshuler ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Proteomic Analysis ◽  
Ischemic Cardiomyopathy ◽  
Border Zone ◽  
Chronic Injury ◽  
Intramyocardial Injection ◽  
Acute Mi ◽  
Hemodynamic Function

Introduction: Mesenchymal Stem Cell (MSC)-derived Extracellular Vesicles (EVs) are an emerging regenerative therapy for treatment of ischemic cardiomyopathy. In this study, we determine the efficacy of MSC-EV therapy in a shear-thinning hydrogel (STG) delivered via intramyocardial injection to the border zone of rat hearts following myocardial infarction (MI). Hypothesis: MSC EV-loaded STGs will preserve hemodynamic function and minimize ventricular scar formation in a rat model of acute MI. Methods: EVs were isolated from MSCs by PEG precipitation, and the EV proteome was characterized by MaxQuant 1.5.1.2 and Metacore analysis software. Varying concentrations of EVs were administered to rats following induction of acute MI by ligation of the left anterior descending artery. EVs were delivered in either sterile phosphate buffered saline (PBS) or STG for sustained EV release. Chronic injury was assessed at 4 weeks post-MI through transthoracic echocardiography, intraventricular pressure-volume loop displacement, and histology. Results: MSC EV proteomic analysis highlighted upregulation of VEGF angiogenic cascades and ILK-mediated proliferative pathways. The mean left ventricle ejection fraction (LVEF) for each treatment group at four weeks is displayed in Table 1. A 20 ug dose of MSC EVs in STG improved LVEF by 19.12% (p<0.05) compared to PBS, with a 90 ug dose of MSC EVs in STG increasing LVEF by 23.56% (p<0.01) (Fig. 1). Conclusions: Intramyocardial injection of MSC EVs in STG post-MI showed concentration dependent improvements in hemodynamics. These findings show that high doses of MSC EV in STG may have potential as a therapy for ischemic cardiomyopathy. Proteomic analysis revealed that angiogenesis, recruitment of cardiac progenitor cells, and immune modulation may be mechanistic drivers of MSC-EV therapy.

Abstract 15413: Building New Arteriogenic Therapy for Ischemic Cardiomyopathyusing Notch-induced Mesenchymal Stem Cell Patch

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shusaku Maeda ◽  
Shigeru Miyagawa ◽  
Takuji Kawamura ◽  
Dai Chida ◽  
Takashi Shibuya ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Notch Signaling ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ischemic Lesion

Introduction: The induction of arteriogenesis is a promising approach for treatment of ischemic cardiomyopathy. Notch signaling has been reported to be a key regulator of arteriogenesis. Hypothesis: We hypothesized that Notch-induced human mesenchymal stem cell (SB623) sheet transplantation would induce arteriogenesis in ischemic lesion, leading to improvement of left ventricular function in ischemic cardiomyopathy model rats. Methods: Two weeks after the ischemic induction, SB623-patches were transplanted to myocardial infarction model rats (SB group, n=10) or shame operations were performed (Control group, n=10). We evaluated cardiac performance and histology six weeks after the treatment in vivo. In vitro, we performed RNA-sequencing of human umbilical vein endothelial cells (HUVECs) cocultured with SB623s. Results: Left ventricular ejection fraction was significantly improved 6 weeks after SB623-sheets transplantation (LVEF, 52±7% vs. 34±5%, p<0.001). Similarly, the attenuation of LV remodeling was observed at 6 weeks (LV diastolic dimension, 73±7 mm vs. 85±5 mm, p<0.001). Histological findings revealed that fibrosis was decreased in SB group (11±1% vs. 22±4%, p=0.02). Furthermore, vWF-positive capillary vessels (vessels, 516±110 /mm 2 vs. 248±26 /mm 2 , p<0.001) and αSMA- and vWF-positive arterioles with over 20μm diameter (arterioles, 25±8 /mm 2 vs. 6±3 /mm 2 , p=0.002) were significantly increased in SB group, suggesting the induction of angiogenesis and arteriogenesis. In vitro, whole transcriptome analysis showed that Notch signaling pathway was significantly upregulated (p<0.001) in HUVECs co-cultured with SB623s. Similarly, pathway analysis revealed upregulated “fluid shear stress and atherosclerosis” pathway (p<0.001) in vitro, suggesting an arteriogenic response of endothelial cell. In vivo study, upregulations of ephrin-B2 (p=0.03) and EphB4 (p=0.01) gene expressions in SB group were confirmed, indicating both arterial and venous remodeling induced by Notch signaling. Conclusions: SB623 patch transplantation induces arteriogenesis with functional recovery via Notch signaling in rat myocardial infarction model, proposing a new strategy for the treatment of ischemic cardiomyopathy.

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