Abstract 717: CGMP Expanded First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVC) Induce Significant Angiogenesis, Myocardial Regeneration and Sustained Functional Recovery Exceeding Older MSC Sources in the Rat Myocardial Infarction (MI) Model

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Száraz Péter ◽  
Alexander Johnston ◽  
Farwah Iqbal ◽  
Banafshe Hoseini ◽  
Alexandra Lucato ◽  
...  
Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Peter Szaraz ◽  
Alexandra Lucato ◽  
Shu Hong Li ◽  
Jun Wu ◽  
Andree Gauthier-Fisher ◽  
...  

Introduction: During myocardial infarction (MI) the ischemic heart muscle loses a substantial number of cells, and a poorly vascularised fibrotic scar forms. We previously showed that local injections of first trimester human umbilical cord perivascular cells (FTM-HUCPVCs) diminish scar tissue and significantly improve cardiac output after MI in rats. Hypothesis: We hypothesised that FTM-HUCPVCs induce superior tissue remodeling and revitalization post-MI by 1: elevating ECM processing gelatinase/collagenase activity, 2: increasing blood vessel penetration and revascularisation of the infarct scar. Methods: MI was induced by left ventricular coronary artery ligation on 8 week old Foxrnu rats. 1 week post-MI, FTM-HUCPVC, term HUCPVC or human BMSC (n=6 per group) were injected into the injured myocardium (3X106 cells each). Histology was performed 2 weeks after cell implantation. In situ gelatinase activity was assessed by fluorescent gelatinase substrate (DQ gelatin). Vascular density was assessed by endothelium-specific fluorescent isolectin (IB4). Fluorescent microscopy images were quantified for vascular density and blood vessel size by ImageJ (6 sections per heart, 9 random fields per section). Statistical analysis: ANOVA. Results: FTM-HUCPVC treatments resulted in increased fluorescent gelatine signal in the scar tissue of post-MI rat hearts (A) and displayed gelatinase activity in a structured pattern. Vascular density of the ischemic myocardium (B) was significantly higher (p<0.01) in FTM- and term HUCPVC treated hearts compared to untreated (C). BMSC treatment did not result in significant improvement. Median area of blood vessel cross-sections was the highest after FTM-HUCPVC treatment and significantly higher (p<0.01) than of BMSC treated hearts. Conclusion: FTM-HUCPVCs induce superior ECM processing and revascularisation in scar tissue after myocardial infarction compared with later gestation HUCPVCs and BMSCs.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Peter Szaraz ◽  
Matthew Librach ◽  
Leila Maghen ◽  
Farwah Iqbal ◽  
Tanya A. Barretto ◽  
...  

Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting thatin vitropredifferentiation could be a potential strategy to increase their effectivenessin vivo.


2013 ◽  
Vol 22 (9) ◽  
pp. 1651-1666 ◽  
Author(s):  
Gustavo Yannarelli ◽  
Victor Dayan ◽  
Natalia Pacienza ◽  
Chyan-Jang Lee ◽  
Jeffrey Medin ◽  
...  

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