Dykes Iain M
School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Cardiol Ther. 2017 Dec;6(2):225-237. doi: 10.1007/s40119-017-0091-9. Epub 2017 May 19.
Exosomes are small, extracellular membrane-bound particles that mediate intercellular transport of a cytosolic cargo. Exosomal transfer of micro-RNA can modify gene expression in targeted cells. Exosome-based endocrine/paracrine signaling has been shown to be involved in a wide range of physiological processes including those associated with cardiovascular injury and disease, but remains relatively poorly understood. Exosomes offer great potential to the clinical field, with applications in both diagnostics and therapeutics. A stable, circulating form of micro-RNA exists in blood protected from endogenous nucleases. This population of micro-RNA, which includes both exosomal and non-exosomal fractions, may be isolated from blood and exploited as a novel disease biomarker with the potential to deliver increased specificity and rapid diagnosis compared to conventional biomarkers. Exosomes also offer a natural drug-delivery vehicle, providing immune evasion and specific targeting through engineering of surface-displayed ligands. Much of the cardioprotective and regenerative benefits of stem-cell grafts are now thought to derive from paracrine signaling rather than direct tissue incorporation and therefore stem cell-derived exosomes offer the potential for a convenient cell-free therapeutic option, eliminating many of the risks and variability associated with stem-cell therapy. In this review, we consider the potential applications of this emerging field to cardiovascular medicine, taking myocardial infarction as our primary example.
外泌体是一种小的、细胞外膜结合颗粒,介导细胞溶质货物的细胞间运输。微小RNA的外泌体转移可改变靶细胞中的基因表达。基于外泌体的内分泌/旁分泌信号已被证明参与广泛的生理过程,包括与心血管损伤和疾病相关的过程,但仍相对了解较少。外泌体在临床领域具有巨大潜力,可应用于诊断和治疗。血液中存在一种稳定的、循环形式的微小RNA,可免受内源性核酸酶的影响。这种微小RNA群体,包括外泌体和非外泌体部分,可从血液中分离出来,并作为一种新型疾病生物标志物加以利用,与传统生物标志物相比,它有可能提供更高的特异性和快速诊断。外泌体还提供了一种天然的药物递送载体,通过对表面展示配体进行工程改造实现免疫逃逸和特异性靶向。现在认为干细胞移植的许多心脏保护和再生益处源于旁分泌信号,而非直接组织整合,因此干细胞衍生的外泌体提供了一种方便的无细胞治疗选择的潜力,消除了与干细胞治疗相关的许多风险和变异性。在本综述中,我们以心肌梗死为例,探讨这一新兴领域在心血管医学中的潜在应用。