RESUMEN
Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI.
Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Infarto del Miocardio , Miocitos Cardíacos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Humanos , Animales , Ratones , Infarto del Miocardio/terapia , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Embrionarias/metabolismo , Células Madre Embrionarias/citología , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/metabolismo , Fibroblastos/metabolismo , Masculino , Daño por Reperfusión Miocárdica/terapia , Daño por Reperfusión Miocárdica/metabolismo , Modelos Animales de Enfermedad , Neovascularización Fisiológica , Células CultivadasRESUMEN
A task force has been established by the European Society of Cardiology to investigate the role of progenitor/stem cell therapy in the treatment of cardiovascular disease. This article is the consensus of this group, of what clinical studies are needed in this field, and the challenges to be addressed in the translation of progenitor/stem cell biology to repair of the heart.