Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis

2004 ◽  
Vol 287 (6) ◽  
pp. H2670-H2676 ◽  
Author(s):  
Noritoshi Nagaya ◽  
Takafumi Fujii ◽  
Takashi Iwase ◽  
Hajime Ohgushi ◽  
Takefumi Itoh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Intravenous Administration ◽  
Diastolic Pressure ◽  
Troponin T ◽  
Left Ventricular ◽  
Control Group

Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into a variety of cells, including cardiomyocytes and endothelial cells. However, little information is available regarding the therapeutic potency of systemically delivered MSCs for myocardial infarction. Accordingly, we investigated whether intravenously transplanted MSCs induce angiogenesis and myogenesis and improve cardiac function in rats with acute myocardial infarction. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. At 3 h after coronary ligation, 5 × 106 MSCs (MSC group, n = 12) or vehicle (control group, n = 12) was intravenously administered to Lewis rats. Transplanted MSCs were preferentially attracted to the infarcted, but not the noninfarcted, myocardium. The engrafted MSCs were positive for cardiac markers: desmin, cardiac troponin T, and connexin43. On the other hand, some of the transplanted MSCs were positive for von Willebrand factor and formed vascular structures. Capillary density was markedly increased after MSC transplantation. Cardiac infarct size was significantly smaller in the MSC than in the control group (24 ± 2 vs. 33 ± 2%, P < 0.05). MSC transplantation decreased left ventricular end-diastolic pressure and increased left ventricular maximum dP/d t (both P < 0.05 vs. control). These results suggest that intravenous administration of MSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium.

Impact of Bone Marrow Mesenchymal Stem Cells That Express Vascular Endothelial Growth Factor on Cardiac Function After Myocardial Infarction

2021 ◽  
Vol 11 (1) ◽  
pp. 44-50
Author(s):  
Yongming He ◽  
Ping Li ◽  
Yunlong Chen ◽  
Youmei Li
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Troponin T ◽  
Gene Transfection ◽  
Control Group ◽  
Marrow Mesenchymal Stem Cells ◽  
The Impact

Transplanted bone marrow mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes and may have the potential to replace necrotic cardiomyocytes resulting from myocardial infarction (MI). Here we established a method for transfection of MSCs with an expression vector encoding human vascular Eedothelial Ggowth Ffctor (hVEGF). We evaluated the impact of transplantation of transfected MSCs on the recovery cardiac function and angiogenesis in a rat model of MI. Rat MSCs were separated by density gradient centrifugation; their specific surface markers were examined as was their ability to differentiate. MSCs were then transfected with pcDNA 3.1-hVEGF 165 or control-containing liposomes. Rats in the experimental MI groups received transfected MSCs, MSCs alone, or gene-transfection alone; controls included a no intervention MI group and a group that was not subjected to ischemia. Among the results, MSCs were successfully isolated and cultured. Among the intervention groups, those that received transplantation of MSCs expressing hVEGF 165 included the smallest areas of infarction and demonstrated the best recovery of cardiac function overall. Moreover, capillary density detected in this group was significantly greater than in the control group and likewise greater than in rats transplanted with MSCs alone. BrdU and Troponin-T staining revealed differential increases in the number of viable cardiomyocytes within the infarction areas; some cardiomyocytes were double-positive. Likewise, evaluation using RT-PCR revealed higher expression levels of hVEGF in rats transplanted with transfected cells compared to those treated with gene transfection alone.

scholarly journals Dynamic Tracking of Injected Mesenchymal Stem Cells after Myocardial Infarction in Rats: A Serial 7T MRI Study

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiuyu Chen ◽  
Minjie Lu ◽  
Ning Ma ◽  
Gang Yin ◽  
Chen Cui ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cine Mri ◽  
Control Group

Purpose.To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner.Materials and Methods.Male MSCs (2 × 106/50 μL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively.Results.MR hypointensities caused by MPIOs were observed on T2⁎-weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation.Conclusions.Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI.

Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction

2007 ◽  
Vol 293 (4) ◽  
pp. H2438-H2447 ◽  
Author(s):  
Robert W. Grauss ◽  
Elizabeth M. Winter ◽  
John van Tuyn ◽  
Daniël A. Pijnappels ◽  
Rebecca Vicente Steijn ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Human Mscs ◽  
Medium Group

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 × 105cells in 20 μl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/ scid mice. Sham-operated mice were used as the control ( n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 ± 2% vs. 36 ± 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 ± 3% vs. 16 ± 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 ± 0.3% of injected cells) expressed von Willebrand factor (16.9 ± 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.

scholarly journals Mesenchymal stem cells from human amniotic membrane differentiate into cardiomyocytes and endothelial-like cells without improving cardiac function after surgical administration in rat model of chronic heart failure

2019 ◽  
Vol 11 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Fazel Gorjipour ◽  
Ladan Hosseini-Gohari ◽  
Alireza Alizadeh Ghavidel ◽  
Seyed Javad Hajimiresmaiel ◽  
Nasim Naderi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Troponin T ◽  
Left Ventricular ◽  
Border Zone ◽  
Vascular Endothelial ◽  
Tissue Fibrosis

Introduction: Human amnion-derived mesenchymal stem cells (hAMSCs) have been used in the treatment of acute myocardial infarction. In the current study, we investigated the efficacy of hAMSCs for the treatment of chronic model of myocardial ischemia and heart failure (HF) in rats. Methods: Male Wistar rats weighing between 250 to 350 g were randomized into three groups: sham, HF control and HF+hAMSCs. For HF induction, animals were anesthetized and underwent left anterior descending artery ligation. In HF+hAMSCs group, 2×106 cells were injected into the left ventricular muscle four weeks post ischemia in the border zone of the ischemic area. Cardiac function was studied using echocardiography. Masson’s trichrome staining was used for studying tissue fibrosis. Cells were transduced with green fluorescent protein (GFP) coding lentiviral vector. Immunohistochemistry was used for detecting GFP, vascular-endothelial growth factor (VEGF) and troponin T markers in the tissue sections. Results: Assessment of the cardiac function revealed no improvement in the myocardial function compared to the control HF group. Moreover, tissue fibrosis was similar in two groups. Immunohistochemical study revealed the homing of the injected hAMSCs to the myocardium. Cells were stained positive for VEGF and troponin T markers. Conclusion: injection of hAMSCs 4 weeks after ischemia does not improve cardiac function and cardiac muscle fibrosis, although the cells show markers of differentiation into vascular endothelial cells and cardiomyocytes. In sum, it appears that hAMSCs are effective in the early phases of myocardial ischemia and does not offer a significant advantage in patients with chronic HF.

Bone Marrow Stem Cells Infusion in Treatment of Patients with Acute Myocardial Infarction.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1682-1682
Author(s):  
Lidia Gil ◽  
Anna Czyz ◽  
Krzysztof Sawinski ◽  
Maria Kozlowska-Skrzypczak ◽  
Mieczyslaw Komarnicki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Control Group ◽  
Acute Pulmonary Oedema ◽  
Autologous Plasma

Abstract Experimental and clinical data show that bone marrow-derived stem cells (BMSC) can contribute to myocardial regeneration after ischemic injury. We present results of intracoronary infusion of autologous BMSCs in treatment of patients (pts) with acute myocardial infarction (MI). 36 pts with first, anterior wall MI, successfully treated with percutaneous coronary angioplasty were enrolled into the study. 24 pts, aged 50.1±9.05 yrs received intracoronary BMSC infusion 4 to 7 days after MI. Control group consisted of 12 pts, aged 51.6±8.7 yrs. In BMSC group BM in total volume 80 (50–150) ml was collected from iliac crest to buffered saline with heparine. After isolation and 18–24 hrs cultivation BMSCs were resuspended in autologous plasma in final volume 12.25±2.05 ml. The mean number of MNC, CD34+, CD133+/CD45+ and CD133+/CD45− cells were respectively: 0.41±0.18x10e9, 3.89±1.45x10e6, 0.96±0.6x10e6, 0.15±0.1x10e6. Transplanted material was divided into 3–5 portion and injected directly to infarcted area (Strauer method). Left ventricular function was evaluated by echocardiography (contactility index, CI), Tc-99 MIBI SPECT (perfusion index, PI) at rest (R) and with dipiridamol (D) and radionuclide ventriculography (ejection fraction, EF) at baseline and after 3, 6, 12 months (mo). CI and PI were assessed in left ventricle and infarct related artery (IRA) area. Control coronary angiography was performed after 6 mo. No adverse effects of BM aspiration in early MI were observed. One pts revealed chills and fever and 1 acute pulmonary oedema after cell infusion. Control angiography revealed restenosis in 3 pts from BMSC and 2 from control group. Results of cardiac test are presented in table. Conclusions: Intracoronary autologous BMNCs transplantation is safe and feasible. Improvement of left ventricular function was observed in BMSC group, mainly concerning perfusion. No accelerated atherosclerosis was seen after intracoronary BMSC administration. Results of cardiac tests BMSC group Control group p CI/CI-IRA 7 day 1.62±0.19/2.3±0.36 1.6±0.24/2.21±0.41 ns CI/CI-IRA 3 mo 1.55±0.2/2.12±0.4 1.65±0.3/2.34±0.64 ns CI/CI-IRA 6 mo 1.5±0.2/2.16±0.37 1.7±0.29/2.46±0.51 0.02 CI/CI-IRA 12 mo 1.55±0.2/2.24±0.44 1.72±0.33/2.48±0.51 ns Pi/PI-IRA-R 10 day 2.45±0.63/2.96±0.88 2.45±0.53/3.04±0.74 ns PI/PI-IRA-R 3 mo 2.25±0.37/2.79±0.61 2.36±0.44/2.88±0.61 ns PI/PI-IRA-R 6 mo 2.19±0.43/2.68±0.67 2.43±0.32/3.02±0.45 0.07 PI/PI-IRA-R 12 mo 2.11±0.33/2.63±0.46 2.36±0.31/2.98±0.46 ns PI/PI-IRA-D 10 day 2.45±0.63/2.96±0.88 2.45±0.53/3.04±0.74 ns PI/PI-IRA-D 3 mo 2.3±0.42/2.87±0.67 2.43±0.4/2.93±0.44 ns PI/PI-IRA-D 6 mo 2.2±0.44/2.58±0.83 2.48±0.43/3.12±0.48 0.06 PI/PI-IRA-D 12 mo 2.16±0.43/2.59±0.6 2.57±0.44/3.35±0.42 0.009 EF 4 day 45.0±7.9 41.6±6.6 ns EF 6 mo 48.2±9.2 42.1±11.4 0.07 EF 12 mo 48.5±4.9 38.9±7.7 0.002

P5397Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Cheng ◽  
X Y Song ◽  
L Chen ◽  
R D Xu ◽  
Q Qin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Conditioned Medium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Paracrine Effect

Abstract Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210 Background A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes. Purpose The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210. Methods and results The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling. Conclusion Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia. Acknowledgement/Funding National Natural Science Foundation of China (Grant Nos. 81470467)

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