Details

Autor(en) / Beteiligte

• Renault, Nisa
• Kervadec, Anaïs
• Bellamy, Valérie
• El Harane, Nadia
• Thiebault, Léa
• Nematalla, Hany
• Pidial, Laetitia
• Lemitre, Mathilde
• Cagnard, Nicolas
• Smit, Nicoline
• Meijborg, Veronique
• Brunaud, Camille
• Renault, Marc
• Colas, Alexandre
• Hagège, Albert
• Coronel, Ruben
• Mercola, Mark
• Silvestre, Jean-Sébastien
• Menasché, Philippe

Titel

Abstract 16533: Extracellular Vesicles Secreted by Human Cardiac Progenitors Are an Effective Alternative to Cell Transplantation for Chronic Heart Failure

Ist Teil von

• Circulation (New York, N.Y.), 2016-11, Vol.134 (Suppl_1 Suppl 1), p.A16533-A16533

Ort / Verlag

by the American College of Cardiology Foundation and the American Heart Association, Inc

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• IntroductionExtracellular vesicles (EV) seem to mediate the benefits of cell therapy for ischemic heart failure (IHF) but the best cellular source of EV and their mechanism of action remain unresolved.MethodsEV secreted by human induced pluripotent stem cell-derived cardiac progenitors (CPg) were isolated by ultracentrifugation. Myocardial infarction was induced in nude mice (permanent LAD occlusion). Three weeks later, mice with LVEF ≤ 45% received transcutaneous echo-guided injections in the peri-infarct myocardium of CPg (1.4x10, n=17), EV secreted by CPg (same batch) over 48 hr (n=19) or PBS (control, n=17). Six weeks later, hearts were blindly evaluated by echocardiography, histology and gene expression profiling. In parallel, in vitro bio-activity assays were developed to determine if fluorescently labelled EV were internalized in cultured rat cardiomyocytes (CM) and could affect their biology following serum deprivation. CPg and EV miRNA content was also assessed by miR arrays.ResultsIn contrast to CPg or PBS, EV significantly improved cardiac function, as evidenced by decreased LV volumes (LVESV-11%, p<0.001; LVEDV-4%, p=0.002) and increased LVEF (+14%, p<0.0001) relative to baseline values. Of note, whereas the functional response of mice to CPg treatment was variable, EV yielded a significantly more homogeneous improvement (comparison of variancesp = 0.06). Differential gene expression analysis of treated hearts showed an enrichment for genes associated with increased cell growth, proliferation and survival in the EV group. In vitro, EV were internalized by CM, induced a dose-dependent increase in CM viability and proliferation and partially restored the stress-induced impairment of CM conduction velocity in multielectrode array experiments. Among the 101 most abundant EV-miR, 12 were highly conserved across species, of which 8 targeted pathways similarly endowed with a tissue-repair potential (cell differentiation, survival, proliferation).ConclusionshiPS-CPg-derived EV are effective in IHF treatment, possibly, in part, through EV-mediated miR transfer fostering endogenous cardiac repair. Their benefits in terms of scale-up and regulation could make them effective substitutes for cell transplantation.