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.

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 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

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.

Predictors of Left Ventricular Remodeling Post Acute Myocardial Infarction. Protocol for a Clinical Study

2019 ◽  
Vol 4 (3) ◽  
pp. 120-123
Author(s):  
Ioana Cîrneală ◽  
Diana Opincariu ◽  
István Kovács ◽  
Monica Chițu ◽  
Imre Benedek
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Speckle Tracking ◽  
Ventricular Remodeling ◽  
Speckle Tracking Echocardiography ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Serum Biomarkers ◽  
Remodeling Index

Abstract Heart failure is a clinical syndrome that appears as a consequence of a structural disease, and the most common cause of left ventricular systolic dysfunction results from myocardial ischemia. Cardiac remodeling and neuroendocrine activation are the major compensatory mechanisms in heart failure. The main objective of the study is to identify the association between serum biomarkers illustrating the extent of myocardial necrosis (highly sensitive troponin as-says), left ventricular dysfunction (NT-proBNP), and systemic inflammatory response (illustrated via serum levels of hsCRP and interleukins) during the acute phase of a myocardial infarction, and the left ventricular remodeling process at 6 months following the acute event, quantified via speckle tracking echocardiography. The study will include 400 patients diagnosed with acute myocardial infarction without signs and symptoms of heart failure at the time of enrollment that will undergo a complex clinical examination and speckle tracking echocardiography. Serum samples from the peripheral blood will be collected in order to determine the inflammatory serum biomarkers. After 6 months, patients will be divided into 2 groups according to the development of ventricular remodeling, quantified by speckle tracking echocardiography: group 1 will consist of patients with a remodeling index lower than 15%, and group 2 will consist of patients with a remodeling index higher than 15%. All clinical and imaging data obtained at the baseline will be compared between these two groups in order to determine the features associated with a higher risk of deleterious ventricular remodeling and heart failure.

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