Somiya Masaharu
Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki, 567-0047, Japan.
J Cell Commun Signal. 2020 Jun;14(2):135-146. doi: 10.1007/s12079-020-00552-9. Epub 2020 Feb 14.
It is widely believed that extracellular vesicles (EVs) mediate intercellular communications by functioning as messengers. EVs contain various biomolecules, including nucleic acids and proteins, as cargo in the internal space. Thus, it has been postulated that this cargo can be transferred from donor cells to recipient cells, leading to phenotypic changes in the recipient cells. However, there is a lack of experimental evidence for the aforementioned hypothesis, that EVs function as messengers. This is presumably because of a lack of rigorous methodologies for EV research. Although cells usually incorporate nanoparticles (NPs) from the extracellular space via endocytosis, these NPs are processed through the endo/lysosomal system and do not escape to the cytoplasm unless they disrupt or fuse with the endo/lysosomal membrane. Whether EVs actually are capable of escaping endo/lysosomes is still debatable. In contrast, viruses have evolved to efficiently deliver their cargo (viral proteins and genetic material) into the cytoplasm of host (recipient) cells by circumventing endo/lysosomal degradation. Thus, it may be helpful to compare EVs to viruses in terms of cargo delivery. The present technological issues that hinder obtaining support for the "EV cargo transfer hypothesis" are summarized and potential solutions for EV research are proposed.
人们普遍认为，细胞外囊泡（EVs）作为信使介导细胞间通讯。EVs在其内部空间包含各种生物分子，包括核酸和蛋白质作为货物。因此，据推测这种货物可以从供体细胞转移到受体细胞，导致受体细胞的表型变化。然而，上述关于EVs作为信使发挥作用的假设缺乏实验证据。这大概是因为缺乏用于EV研究的严格方法。虽然细胞通常通过内吞作用从细胞外空间摄取纳米颗粒（NPs），但这些NPs通过内吞/溶酶体系统进行处理，除非它们破坏或与内吞/溶酶体膜融合，否则不会逃逸到细胞质中。EVs是否真的能够逃离内吞/溶酶体仍有争议。相比之下，病毒已经进化到通过规避内吞/溶酶体降解将其货物（病毒蛋白和遗传物质）有效地递送到宿主（受体）细胞的细胞质中。因此，在货物递送方面将EVs与病毒进行比较可能会有所帮助。总结了目前阻碍获得对“EV货物转移假说”支持的技术问题，并提出了EV研究的潜在解决方案。
