P1646Do Extracellular Vesicles repair chronic ischemic heart disease by replenishing the cardiomyocyte pool?
| العنوان: | P1646Do Extracellular Vesicles repair chronic ischemic heart disease by replenishing the cardiomyocyte pool? |
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| المؤلفون: | Manon Desgres, Maria Perotto, Jean-Sébastien Silvestre, B. Lima Correa, Marie Cécile Perier, N. El Harane, Valérie Bellamy, Philippe Menasché, E Barron, Nisa Renault, Massimiliano Gnecchi, Laetitia Pidial, noemie tence |
| المصدر: | European Heart Journal. 40 |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Pathology, medicine.medical_specialty, business.industry, medicine, Cardiology and Cardiovascular Medicine, business, Extracellular vesicles, Chronic ischemic heart disease |
| الوصف: | Introduction Extracellular Vesicles (EV) seem to mediate the benefits of cell therapy for ischemic heart failure. Although their mechanism of action remains poorly understood, one hypothesis is that they might trigger the generation of new cardiomyocytes. The doubly transgenic fate-mapping MerCreMer/ZEG mice model was thus used to distinguish whether these putative new cardiomyocytes originated from the division of preexisting ones (GFP+, Troponin T [TnT+], EdU+) or differentiated from endogenous progenitors, in which case they would stain positive for TnT+/EdU+ but negative for GFP. Methods Myocardial infarction was induced in 35 MerCreMer/ZEG mice by permanent occlusion of the left anterior descending coronary artery. Three weeks later, the surviving mice (n=18) with a left ventricular ejection fraction (LVEF) ≤45% received transcutaneous echo-guided injections in the peri-infarct myocardium of either EV (from 1.4 million human iPS-derived cardiovascular progenitor cells; 10 billion particles, n=9) or PBS (n=9); osmotic pumps were implanted to deliver EdU for 7 days in order to track the proliferation of new and native cardiomyocytes. Four-6 weeks after treatment all mice were evaluated by echocardiography (n=9 per group) and MRI (7 in each group), and then sacrificed for histological assessment, blindly. Results Based on echocardiography (MRI data pending), EV improved LVEF by 16% relative to baseline while a decrease of 4% was observed in the PBS group (p=0.46). The number of new cardiomyocytes (TnT+/EdU+/GFP+) did not significantly differ between the EV-treated hearts and the controls, and averaged 0.54% of the total heart cell content in infarct, peri-infarct and remote areas. However, EV treatment better preserved preexisting GFP+/WGA+/TnT+ cardiomyocytes in the peri-infarct area as their number was greater by 5.15% compared to PBS (32 sections analyzed for each mouse). Compared to the PBS control group, EV delivery was also associated with a 2.5% decrease in fibrosis, a reduction of infarct size by 14.9%, and an increase in angiogenesis in the peri-infarct area (with a between-group absolute difference of 71 capillaries, on the basis of isolectin staining). Conclusions EV secreted by iPS-derived cardiovascular progenitors improve the function of chronically infarcted hearts. Preservation of the existing cardiomyocyte pool and limitation of adverse remodeling and scarred tissue, likely favored by increased neoangiogenesis, are the main mechanisms mediated by the EV, while fate mapping allowed to exclude the generation of new cardiomyocytes. |
| تدمد: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehz748.0405 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::f907babd46a017d2ba389e5567ae8501 https://doi.org/10.1093/eurheartj/ehz748.0405 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........f907babd46a017d2ba389e5567ae8501 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15229645 0195668X |
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| DOI: | 10.1093/eurheartj/ehz748.0405 |