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.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

The Reverse Remodeling Effect of Mesenchymal Stem Cells is Independent from the Site of Epimyocardial Cell Transplantation

2013 ◽  
Vol 8 (6) ◽  
pp. 433-439 ◽  
Author(s):  
Mani Arsalan ◽  
Stefan Dhein ◽  
Heike Aupperle ◽  
Ardawan Julian Rastan ◽  
Markus Jan Barten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sham Group ◽  
Heart Function ◽  
Capillary Density ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Control Group ◽  
Positive Effects ◽  
Significant Difference

Objective The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)–induced failing hearts. Methods Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. Results The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups ( P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups ( P = 0.927). Conclusions Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.

Abstract P393: Fabrication Of Immunomodulatory Hydrogels For Cardiac Repair After Acute Myocardial Infaction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Weiang Yan ◽  
Alireza Rafieerad ◽  
Abhay D Srivastava ◽  
Keshav Narayan Alagarsamy ◽  
Rakesh C Arora ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
T Lymphocytes ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Cardiac Repair ◽  
Regulatory T Lymphocytes ◽  
Ifn Γ ◽  
Chitosan Hydrogels

Introduction: The balance of pro- and anti-inflammatory processes is tightly linked to left ventricular remodeling after myocardial infarction. Immune activation also plays a key role in rejection of transplanted allogeneic stem cells. In this study, we present the design, fabrication and characterization of immunomodulatory chitosan-based hydrogels for cardiac repair after myocardial infarction. Methods: Chitosan hydrogels conjugated with small immunomodulatory molecules were synthesized through a thermogelation process. Resultant hydrogels were characterized using scanning electron microscopy and Fourier-transformed infrared spectroscopy. Human mesenchymal stem cells were encapsulated into the hydrogels and biocompatibility was assessed after one week using fluorescence microscopy and a colorimetric assay. Immunomodulatory activity was assessed after co-culture with human T-lymphocytes using flow cytometry for CD4+IFN-γ+ pro-inflammatory and CD4+CD25+FoxP3+ regulatory T-lymphocytes. Results: Small immunomodulatory molecules were successfully integrated into chitosan hydrogels. Physico-chemical characterization revealed no significant changes to the 3D structure and porosity of hydrogels. The addition of 10μM atorvastatin or 10μM rosuvastatin did not result in significant cytotoxicity to encapsulated mesenchymal stem cells at 3 or 7 days. Addition of statins resulted in marked suppression of CD4+ T-lymphocyte proliferation (Control 25.1 Fold, Atorvastatin 1.0 Fold, Rosuvastatin 2.3 Fold, p<0.001) and activation (CD4+IFN-γ+ Population: Control 87.1%, Rosuvastatin 23.7%, p<0.001) after stimulation. No differences were seen in percentages of CD4+CD25+FoxP3+ regulatory T-lymphocytes (Control 5.5%, Rosuvastatin 5.7%, ns). Conclusion: A biocompatible immunomodulatory hydrogel was created through integration of atorvastatin and rosuvastatin into a chitosan hydrogel. Experiments are currently underway in vivo to examine its usefulness for stem cell delivery and reducing adverse left ventricular remodeling after myocardial infarction.

Abstract 11460: Chronic Intermittent Low Level Transcutaneous Electrical Stimulation of the Auricular Branch of the Vagus Nerve Improves Left Ventricular Remodeling in Conscious Dogs With Healed Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Zhuo Wang ◽  
Lilei Yu ◽  
Songyun Wang ◽  
Bing Huang ◽  
Kai Liao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Vagus Nerve ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Control Group ◽  
Low Level ◽  
Auricular Branch

Introduction: Vagus nerve stimulation (VNS) attenuates left ventricular remodeling after myocardial infarction (MI) by improving the imbalance of autonomic nervous system. Our previous study found Low-level tragus stimulation (LL-TS) had the same antiarrhythmic effects as VNS by regulation of the autonomic nervous system. Hypothesis: Chronic intermittent LL-TS could attenuate left ventricular remodeling in conscious dogs with healed myocardial infarction. Methods: Thirty beagle dogs were randomly divided into three groups. LL-TS group (n=10) and MI group (n=10) underwent left anterior descending coronary artery and all major diagonal branches ligation to introduce MI under general anesthesia. Control group (n=10) underwent sham surgery. Auricular vagus nerve stimulation (frequency 20Hz, pulse width 1ms) with duty cycle of 5s on and 5s off was delivered to the bilateral tragus in external auditory canal with ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold for setting LL-TS at 80% below that. The actual voltage of stimulation was in the range of 16 to 24V that did not cause any heart rate changes. LL-TS group was given four hours of LL-TS at 7-9AM and 4-6PM on conscious dogs from the day of MI introduction to the end of 90-day follow-up, MI group and control group were given no stimulations. Results: At the end of 90-days follow-up LL-TS group significantly reduced left ventricular dilatation, improve left ventricular contractile and diastolic function, reduced mean infarct size by about 50% compared with MI group. Also LL-TS treatment alleviated cardiac fibrosis around infarction border and significantly decreased protein level of collagen I, collagen III, TGF-β1, MMP-9 in noninfarcted left ventricular free wall tissue after MI. Moreover, the plasma level of hs-CRP, NE and NT-proBNP in LL-TS group was significantly lower than MI group from the 7th day to the end of follow-up. Conclusions: Chronic intermittent low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve can attenuate left ventricular remodeling and improve cardiac function in conscious dogs with healed myocardial infarction.

scholarly journals Effect of Cardiac Stem Cells on Left-Ventricular Remodeling in a Canine Model of Chronic Myocardial Infarction

2013 ◽  
Vol 6 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Frederick G.P. Welt ◽  
Robert Gallegos ◽  
John Connell ◽  
Jan Kajstura ◽  
Domenico D’Amario ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Canine Model ◽  
Left Ventricular ◽  
Cardiac Stem Cells ◽  
Chronic Myocardial Infarction

Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction

2017 ◽  
Vol 112 (3) ◽  
Author(s):  
Thomas Ravn Lassen ◽  
Jan Møller Nielsen ◽  
Jacob Johnsen ◽  
Steffen Ringgaard ◽  
Hans Erik Bøtker ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Rat Model ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular

scholarly journals Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Hüseyin Ince ◽  
Michael Petzsch ◽  
Hans Dieter Kleine ◽  
Heike Eckard ◽  
Tim Rehders ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Primary Pci ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Background— Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown. Methods and Results— Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85±30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 μg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, β-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC CD34+ ), with a 20-fold increase (from 3±2 at baseline to 66±54 MNC CD34+ /μL on day 6; P <0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF–induced MNC CD34+ mobilization led to enhanced resting wall thickening in the infarct zone of 1.16±0.29 mm ( P <0.05 versus control), which was sustained at 1.20±0.28 after 12 months ( P <0.001 versus control). Similarly, left ventricular ejection fraction improved from 48±4% at baseline to 54±8% at 4 months ( P <0.005 versus control) and 56±9% at 12 months ( P <0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70±0.22 to 1.42±0.26 and 1.33±0.21 at 4 and 12 months, respectively), after G-CSF ( P <0.05 versus baseline and P <0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55±4 mm at baseline to 58±4 mm ( P <0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function. Conclusion— Mobilization of MNC CD34+ by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.

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