Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Int J Mol Sci. 2019 Mar 18;20(6):1349. doi: 10.3390/ijms20061349.
The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications.
过去十年中，人们对细胞释放的细胞外囊泡（EVs）产生了浓厚的兴趣，并提出它们在生理和病理条件下介导细胞间通讯。由于 EVs 的遗传内容反映了其各自亲代细胞的遗传内容，许多研究人员已将 EVs 作为各种疾病生物标志物的来源。到目前为止，给定 EV 样本的异质性问题在实验水平上很少得到解决。由于其相对较小的尺寸，EVs 在给定的样本中很难可靠地分离和检测。因此，尽管该领域最近取得了进展，但仍缺乏针对 EV 进行准确特征描述的标准化方案。尽管在分析前参数方面不断取得进步，但可以更有效地评估 EVs，然而，缺乏从背景中更客观地区分 EVs 的方法，以及解释多个单一 EV 参数的方法。在这里，我们根据 EV 的起源、释放方式、膜组成、细胞器和生化内容以及其他因素来综述其异质性。在此过程中，我们还概述了目前可用于单 EV 分析的方法和潜在的应用方法。最后，我们研究了在单 EV 水平上分析该问题的最新实验结果，并讨论了潜在的影响。
