De Toro Julieta, Herschlik Leticia, Waldner Claudia, Mongini Claudia
Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires , Buenos Aires , Argentina.
Front Immunol. 2015 May 4;6:203. doi: 10.3389/fimmu.2015.00203. eCollection 2015.
From the time when they were first described in the 1970s by the group of Johnstone and Stahl, exosomes are a target of constant research. Exosomes belong to the family of nanovesicles which are of great interest for their many functions and potential for diagnosis and therapy in multiples diseases. Exosomes originate from the intraluminal vesicles of late endosomal compartments named multivesicular bodies and the fusion of these late endosomes with the cell membrane result in the release of the vesicles into the extracellular compartment. Moreover, their generation can be induced by many factors including extracellular stimuli, such as microbial attack and other stress conditions. The primary role attributed to exosomes was the removal of unnecessary proteins from the cells. Now, several studies have demonstrated that exosomes are involved in cell-cell communication, even though their biological function is not completely clear. The participation of exosomes in cancer is the field of microvesicle research that has expanded more over the last years. Evidence proving that exosomes derived from tumor-pulsed dendritic cells, neoplastic cells, and malignant effusions are able to present antigens to T-cells, has led to numerous studies using them as cell-free cancer vaccines. Because exosomes derive from all cell types, they contain proteins, lipids, and micro RNA capable of regulating a variety of target genes. Much research is being conducted, which focuses on the employment of these vesicles as biomarkers in the diagnosis of cancer in addition to innovative biomarkers for diagnosis, prognosis, and management of cardiovascular diseases. Interesting findings indicating the role of exosomes in the pathogenesis of several diseases have encouraged researchers to consider their therapeutic potential not only in oncology but also in the treatment of autoimmune syndromes and neurodegenerative disorders such as Alzheimer's and Parkinson's disease, in addition to infectious diseases such as tuberculosis, diphtheria, and toxoplasmosis as well as infections caused by prions or viruses such as HIV. The aim of this review is to disclose the emerging roles of exosomes in normal and pathological conditions and to discuss their potential therapeutic applications.
自20世纪70年代被约翰斯通和施塔尔团队首次描述以来，外泌体一直是持续研究的对象。外泌体属于纳米囊泡家族，因其多种功能以及在多种疾病诊断和治疗方面的潜力而备受关注。外泌体起源于晚期内体区室（称为多囊泡体）的腔内囊泡，这些晚期内体与细胞膜融合导致囊泡释放到细胞外区室。此外，包括细胞外刺激（如微生物攻击和其他应激条件）在内的许多因素均可诱导其产生。外泌体最初被认为的主要作用是清除细胞中不必要的蛋白质。现在，多项研究表明外泌体参与细胞间通讯，尽管其生物学功能尚不完全清楚。外泌体在癌症中的作用是过去几年中微囊泡研究扩展得最多的领域。有证据表明，源自肿瘤脉冲树突状细胞、肿瘤细胞和恶性积液的外泌体能够将抗原呈递给T细胞，这促使众多研究将其用作无细胞癌症疫苗。由于外泌体源自所有细胞类型，它们含有能够调节多种靶基因的蛋白质、脂质和微小RNA。目前正在进行大量研究，除了将这些囊泡用作癌症诊断的生物标志物外，还关注其作为心血管疾病诊断、预后和管理的创新生物标志物的应用。有趣的研究结果表明外泌体在多种疾病的发病机制中发挥作用，这鼓励研究人员不仅考虑其在肿瘤学中的治疗潜力，还考虑其在自身免疫综合征和神经退行性疾病（如阿尔茨海默病和帕金森病）治疗中的潜力，此外还包括结核病和白喉等传染病、弓形虫病以及朊病毒或HIV等病毒引起的感染。本综述的目的是揭示外泌体在正常和病理条件下的新作用，并讨论其潜在的治疗应用。
