Hernán González-King, Patricia G. Rodrigues, Tamsin Albery, Benyapa Tangruksa, Ramya Gurrapu, Andreia M. Silva, Gentian Musa, Dominika Kardasz, Kai Liu, Bengt Kull, Karin Åvall, Katarina Rydén-Markinhuhta, Tania Incitti, Nitin Sharma, Cecilia Graneli, Hadi Valadi, Kasparas Petkevicius, Miguel Carracedo, Sandra Tejedor, Alena Ivanova, Sepideh Heydarkhan-Hagvall, Phillipe Menasché, Jane Synnergren, Niek Dekker, Qing-Dong Wang, Karin Jennbacken
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引用次数: 0
摘要
在心肌梗塞(MI)的临床前模型中,来自不同细胞来源的小细胞外囊泡(sEV)已被证明能增强心脏功能。本研究的目的是比较不同来源的 sEV 对心脏修复的作用,并确定最有效的 sEV。我们在体外心脏修复模型中全面评估了从人类原代骨髓间充质基质细胞(BM-MSC)、人类永生化间充质干细胞(hTERT-MSC)、人类胚胎干细胞(ESC)、ESC衍生的心脏祖细胞(CPC)、人类ESC衍生的心肌细胞(CM)和人类原代心室成纤维细胞(VCF)中获得的sEV的功效。ESC衍生的sEV(ESC-sEV)在体外表现出最佳的促血管生成和抗纤维化效果。然后,我们在小鼠心肌缺血再灌注损伤(IRI)模型中评估了体外表现最出色的 sEV 的功能,并分析了它们的 RNA 和蛋白质组成。在体内,ESC-sEV 通过下调纤维化和增加血管生成来减少不良的心脏重塑,从而在心肌梗死后提供最有利的结果。此外,从 hTERT-MSC、ESC 和 CPC 中提取的 sEV 的转录组和蛋白质组特征揭示了 ESC-sEV 中可能驱动所观察到的功能的因素。总之,ESC-sEV 作为一种无细胞疗法,在促进心肌梗死后的心脏修复方面大有可为。
Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair: Superiority of embryonic stem cells
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.
期刊介绍:
The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies.
The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.