外泌体源性miRNA在肿瘤发生发展中作用的研究进展

外泌体作为细胞间信息交流的重要媒介,可携带蛋白质、脂质、核酸等多种信息物质到受体细胞中,使受体细胞产生不同的生化反应进而调节各项生命活动。近年来大量研究表明,外泌体源性miRNA广泛参与包括肿瘤在内的多种疾病的发生发展。为了更好地了解外泌体源性miRNA对肿瘤发生发展的影响,该文综述了外泌体源性miRNA在肿瘤血管生成、上皮-间质转化、免疫调节、转移前微环境、耐药等方面的作用。     

间充质干细胞外泌体经不同信号通路调节骨代谢的研究进展

间充质干细胞外泌体(mesenchymal stem cell exocrines,MSC-EXOs)由间充质干细胞(mesenchymal stem cells,MSCs)释放，具有旁分泌作用的囊泡。MSC-EXOs可以通过传递细胞因子来介导细胞间通讯从而调节受体细胞的细胞行为。目前，已有许多研究发现，MSC-EXOs可以通过传递细胞因子介入骨代谢相关信号通路来调节骨代谢。本文对间充质干细胞外泌体调节骨代谢的主要信号通路内容及作用的研究进展进行综述总结，并讨论了外泌体中重要细胞因子的作用，旨在找寻MSCEXOs治疗骨代谢相关疾病新的治疗靶点。     

间充质干细胞来源的外泌体在自身免疫性疾病中的治疗作用（英文）

自身免疫性疾病往往累及多个器官,可以引起多种并发症。近年来,自身免疫性疾病的新疗法被广泛提出,而间充质干细胞(mesenchymal stem cells, MSCs)因其独特的免疫调节能力成为了研究热点。外泌体是MSCs等细胞分泌的一种小囊泡,通过携带蛋白质、mRNA、microRNA、脂质等细胞内容物,参与细胞间物质和信息的传递,调节受体细胞的生物学功能,这可能是MSCs免疫调节功能的潜在机制。越来越多的研究表明,MSCs分泌的外泌体具有与MSCs相似甚至更好的免疫调节功能,其在自身免疫性疾病治疗中的作用已在某些疾病的动物模型中得到证实。本综述总结了MSCs及其外泌体对免疫系统和免疫细胞的作用,以及近年来MSCs来源的外泌体在自身免疫性疾病中作用的研究进展。     

骨骼肌组织来源的外泌体促进骨骼肌干细胞增殖并抑制其分化

骨骼肌干细胞(又称为肌卫星细胞)位于肌纤维膜与基底膜之间。肌纤维分泌各种细胞因子到骨骼肌干细胞微环境中,进而调节肌卫星细胞的功能。最近的研究发现,骨骼肌来源的外泌体以内分泌方式影响其他组织的功能,但是,骨骼肌组织分泌的外泌体是否以旁分泌的方式调控肌卫星细胞的功能,目前并不清楚。该研究发现,骨骼肌来源的外泌体能够显著促进肌卫星细胞增殖、抑制其分化,这为揭示外泌体介导的骨骼肌组织微环境调控肌卫星细胞功能提供了实验证据。     

干细胞外泌体在衰老和衰老相关疾病中的作用

随着人口老龄化加剧，衰老及其衰老相关疾病已成为影响生活质量的关键问题。近年来，研究发现干细胞具有抑制炎症、调节免疫反应、预防细胞凋亡、替换和促进受损部位修复等功能。但证据表明，干细胞治疗的效果主要来自干细胞分泌的外泌体。外泌体是由内吞膜衍生而来的纳米级囊泡，包含脂质、蛋白质、核酸和代谢产物等活性物质，是细胞与细胞间通讯的主要参与者。外泌体可以将生物活性物质转移至靶细胞，从而引起靶细胞的表型改变，进而调节器官的修复和再生。表型改变包括防止受体细胞凋亡、诱导靶细胞增殖、刺激免疫调节反应、减小靶细胞氧化应激以及增强氧供应。本文简述了外泌体的生物发生、分泌以及信号传导过程，并重点讨论了在基础研究和临床应用中，不同干细胞来源的外泌体对皮肤衰老和衰老相关疾病(例如心血管疾病、骨关节炎、骨质疏松、阿尔兹海默症)的影响。尽管干细胞外泌体的临床应用仍然存在问题，但它从基础研究到临床应用的前景仍然值得探索，这对于延缓衰老和治疗衰老相关疾病具有重要意义。     

外泌体miRNA的生物学功能及其在肺纤维化疾病中的调控作用

外泌体是一种微型纳米级细胞外囊泡,由于能够直接参与细胞间信息的传递和物质的运输,被认为是细胞间通讯、免疫调节、疾病诊断和预后循环生物学标志物的重要载体,其携带的核酸和蛋白质等内含物能够影响受体细胞的生理状态.作为一种内源性非编码微小RNA,microRNA (miRNA)对疾病诊断和治疗有着重要的研究价值,有大量证据表明该类分子对肺部疾病的发病进程起着控制调节作用.本文聚焦于近年来细胞外泌体来源miRNA的生物学特性和功能领域,综述了近年来生物医学研究中的热点分子外泌体miRNA在肺部疾病尤其是肺纤维化中调控功能和机制的研究,因此不仅能为肺纤维化疾病的诊断提供新的标志物分子,并且还能够为肺纤维化的外泌体干预治疗建议新的干预策略.     

外泌体在肿瘤转移及诊疗中的研究进展

外泌体是直径为40~130 nm的纳米级囊泡结构,其中包含有大量的蛋白质、核酸和脂质等,在细胞间物质信息传递过程中发挥重要的作用。与正常细胞相比,肿瘤细胞释放更多的外泌体,并且其中所包含的一系列蛋白质和核酸组分(包括mi RNAs)在调节肿瘤微环境、促进肿瘤的转移侵袭过程中起到了关键的作用。该文重点介绍了由外泌体所介导的整合蛋白、表皮生长因子受体和mi RNAs等分子在细胞间的转运对于肿瘤转移和侵袭的影响,并展望了外泌体在肿瘤的诊断和治疗方面的应用前景。随着研究的深入,通过外泌体建立有效的早期诊断体系和诊疗方案将为肿瘤的治疗提供新的思路和方法。     

间充质干细胞来源外泌体在膝骨关节炎微环境中的作用

骨关节炎是一种涉及所有关节成分（包括关节软骨、软骨下骨、滑膜、韧带、关节囊和关节周围肌肉）的关节退行性疾病，会导致严重的残疾，其中最常见的是膝骨关节炎（knee osteoarthritis，KOA）。外泌体是一种由不同细胞分泌的直径为40~100 nm的胞外囊泡，可以传递DNA、微小RNA、mRNA、蛋白质等多种物质，并通过多种方式进行细胞间的信息传递和功能调节。间充质干细胞（mesenchymal stem cells，MSCs）可以从骨髓、脂肪、滑膜及外周血等组织分离，是一类具有多向分化潜能的祖细胞，以干细胞为基础的疗法可以修复软骨损伤，对抗KOA的发展，间充质干细胞能够分泌多种营养因子来调节受损的微环境，其中间充质干细胞来源的外泌体被认为在KOA炎症反应及软骨细胞代谢中发挥着重要的作用，其能够调节膝骨关节微环境中B细胞、T细胞、滑膜细胞、软骨细胞代谢及其细胞外基质的分解与合成平衡，维持软骨稳态。近期有多项研究表明，不同组织来源的间充质干细胞外泌体对骨关节炎均有明确的治疗作用，本文就MSCs来源的外泌体治疗KOA的具体机制进行综述，以期对干细胞治疗KOA提供理论依据。     

神经干细胞外泌体—神经疾病治疗的新途径

外泌体(exosomes)几乎由所有类型的细胞释放,不同细胞来源的外泌体携带不同的蛋白质、核酸和脂质,参与细胞间的信息交流。最近的研究表明,神经干细胞(neural stem cells,NSCs)分泌的外泌体可参与神经性疾病生理和病理的变化过程,并发挥其潜在的神经调节和修复功能。因此,NSCs分泌的外泌体可以起到治疗神经系统疾病的作用。该文阐述了外泌体的生物合成,NSCs分泌的外泌体的特性、功能及其治疗神经系统疾病的研究进展;讨论了外泌体在神经系统疾病治疗方面的应用潜力和面临的挑战。     

外泌体与肿瘤关系的研究进展北大核心CSCD

外泌体(又称外秘小体,exosomes)是一种能被多种活细胞分泌,直径为30~100nm,并广泛分布于多种体液中的微囊泡结构。近10年来研究发现外泌体富含蛋白质、DNA、RNA和脂质等生物活性分子,这些物质在肿瘤转移前微环境的形成、侵袭与转移中发挥重要的作用。外泌体以其独特的方式包裹着核酸和蛋白质,在细胞间有效稳定地发挥信息交流的作用。为更好地了解外泌体促进肿瘤发生发展的机制,该文将对外泌体的结构和生物学功能,以及在肿瘤微环境中如何影响肿瘤发生发展进行综述。     

Communication in tiny packages: Exosomes as means of tumor-stroma communication

Tumor-derived exosomes are nano-sized vesicles acting as multi-signal devices influencing tumor growth at local and distant sites. Exosomes are derived from the endolysosomal compartment and can shuttle diverse biomolecules like nucleic acids (microRNAs and DNA fragments), lipids, proteins, and even pharmacological compounds from a donor cell to recipient cells. The transfer of cargo to recipient cells enables tumor-derived exosomes to influence diverse cellular functions like proliferation, cell survival, and migration in recipient cells, highlighting tumor-derived exosomes as important players in communication within the tumor microenvironment and at distant sites. In this review, we discuss the mechanisms associated with exosome biogenesis and cargo sorting. In addition, we highlight the communication of tumor-derived exosomes in the tumor microenvironment during different phases of tumor development, focusing on angiogenesis, immune escape mechanisms, drug resistance, and metastasis.     

Cell to Cell Signalling via Exosomes Through esRNA

Exosomes are small vesicles of endosomal origin that can be released by many different cells to the microenvironment. Exosomes have been shown to participate in the immune system, by mediating antigen presentation. We have recently shown the presence of both mRNA and microRNA in exosomes, specifically in exosomes derived from mast cells. This RNA can be transferred between one mast cell to another, most likely through fusion of the exosome to the recipient cell membrane. The delivered RNA is functional, as the mRNA can lead to translation of new proteins in a recipient cell. The RNA shuttled between cells via exosomes is called esRNA. We propose that several types of exosomes may exist, and that an additional function of exosomes is to communicate to neighboring cells through delivery of RNA-signals.     

肿瘤细胞来源的外泌体与恶性肿瘤的进展及化疗

外泌体是细胞分泌的一种纳米级囊泡结构,在血液、唾液、尿液等多种体液中均有分布.作为一类重要的细胞间通信分子,外泌体含有多种具有生物活性的成分,可通过多种方式在人体中发挥调节作用.目前在多种类型的细胞中均发现外泌体的存在,而肿瘤细胞来源的外泌体由于其本身的特性和功能特点,可通过微环境介导肿瘤细胞的增生、血管形成和免疫耐受,并可通过介导上皮-间质转化（epithelial-mesenchymal transition, EMT）
和胞内药物排斥反应等增加肿瘤细胞的化疗抵抗能力.同时,因其含有肿瘤细胞所分泌的特异性成分,因而可通过对外泌体中相关分子改变的检测,对疾病进行诊断和监测,并可为临床个体化用药提供新思路.     

Cell to Cell Signalling via Exosomes Through esRNA

Exosomes are small vesicles of endosomal origin that can be released by many different cells to the microenvironment. Exosomes have been shown to participate in the immune system, by mediating antigen presentation. We have recently shown the presence of both mRNA and microRNA in exosomes, specifically in exosomes derived from mast cells. This RNA can be transferred between one mast cell to another, most likely through fusion of the exosome to the recipient cell membrane. The delivered RNA is functional, as the mRNA can lead to translation of new proteins in a recipient cell. The RNA shuttled between cells via exosomes is called esRNA. We propose that several types of exosomes may exist, and that an additional function of exosomes is to communicate to neighbouring cells through delivery of RNA-signals.Key words: esRNA, exosomes, microRNA, mRNA, cell communication, signalling     

Exosomes Derived from Squamous Head and Neck Cancer Promote Cell Survival after Ionizing Radiation

Exosomes are nanometer-sized extracellular vesicles that are believed to function as intercellular communicators. Here, we report that exosomes are able to modify the radiation response of the head and neck cancer cell lines BHY and FaDu. Exosomes were isolated from the conditioned medium of irradiated as well as non-irradiated head and neck cancer cells by serial centrifugation. Quantification using NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response of other cells the exosomes were transferred to non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes isolated from both irradiated and non-irradiated cells by irradiated recipient cells compared to non-irradiated recipient cells. Functional analyses by exosome transfer indicated that all exosomes (from non-irradiated and irradiated donor cells) increase the proliferation of non-irradiated recipient cells and the survival of irradiated recipient cells. The survival-promoting effects are more pronounced when exosomes isolated from irradiated compared to non-irradiated donor cells are transferred. A possible mechanism for the increased survival after irradiation could be the increase in DNA double-strand break repair monitored at 6, 8 and 10 h after the transfer of exosomes isolated from irradiated cells. This is abrogated by the destabilization of the exosomes. Our results demonstrate that radiation influences both the abundance and action of exosomes on recipient cells. Exosomes transmit prosurvival effects by promoting the proliferation and radioresistance of head and neck cancer cells. Taken together, this study indicates a functional role of exosomes in the response of tumor cells to radiation exposure within a therapeutic dose range and encourages that exosomes are useful objects of study for a better understanding of tumor radiation response.     

Exosome-derived uterine miR-218 isolated from cows with endometritis regulates the release of cytokines and chemokines

As an inflammation of the endometrium, endometritis can affect fertility and lead to serious economic losses in the dairy industry. Widely found in various tissues and body fluids, exosomes and exosome micro (mi)RNAs have been shown to play an important regulatory role in the immune responses. As one of differentially expressed exosome miRNAs, miR-218 is involved in the pathogenesis of bovine endometritis. The mechanisms of miR-218 in regulating the release of cytokines and chemokines in endometritis, however, are poorly understood. Exosomes were isolated from bovine uterine cavity fluid and verified by transmission electron microscopy. An in vitro lipopolysaccharide-treated cell model for bovine endometritis was then established to evaluate the correlation between exosome-derived miR-218 and the immune responses. We demonstrated that exosomes could be used to deliver miR-218 from endometrial epithelial cells (EECs) into the uterine microenvironment and adjacent recipient cells to modulate local immune responses. miR-218 packaged in the exosomes secreted from EECs acts as an inhibitor by blocking immune factors such as interleukin (IL)-6, IL-1β, tumour necrosis factor-α, the chemokines macrophage inflammatory genes (MIP)-1α and MIP-1β to maintain the immune balance in the uterus. However, uterine inflammation altered the immunoregulatory mechanism of exosome miR-218. MiR-218 is a potential biomarker for the detection of endometritis. Our findings also revealed a new mechanism for the development of endometritis in cows.     

Ionizing Radiation and Glioblastoma Exosomes: Implications in Tumor Biology and Cell Migration

Exosomes are nanometer-sized lipid vesicles released ubiquitously by cells, which have been shown to have a normal physiological role, as well as influence the tumor microenvironment and aid metastasis. Recent studies highlight the ability of exosomes to convey tumor-suppressive and oncogenic mRNAs, microRNAs, and proteins to a receiving cell, subsequently activating downstream signaling pathways and influencing cellular phenotype. Here, we show that radiation increases the abundance of exosomes released by glioblastoma cells and normal astrocytes. Exosomes derived from irradiated cells enhanced the migration of recipient cells, and their molecular profiling revealed an abundance of molecules related to signaling pathways important for cell migration. In particular, connective tissue growth factor (CTGF) mRNA and insulin-like growth factor binding protein 2 (IGFBP2) protein levels were elevated, and coculture of nonirradiated cells with exosomes isolated from irradiated cells increased CTGF protein expression in the recipient cells. Additionally, these exosomes enhanced the activation of neurotrophic tyrosine kinase receptor type 1 (TrkA), focal adhesion kinase, Paxillin, and proto-oncogene tyrosine-protein kinase Src (Src) in recipient cells, molecules involved in cell migration. Collectively, our data suggest that radiation influences exosome abundance, specifically alters their molecular composition, and on uptake, promotes a migratory phenotype.     

A review on the stem cell therapy and an introduction to exosomes as a new tool in reproductive medicine

Stem cell therapy and exosome therapy are the two experimental methods that are now at the center of attention. Various types of stem cells, especially mesenchymal stem cells and spermatogonial stem cells have been widely administrated in reproductive medicine. However, due to the limitation of injecting living cells, using their paracrine secretions such as exosomes seems to be a better option. Exosomes show regenerative, pro-angiogenic, anti-apoptotic, anti-inflammatory, anti-hypoxic, and anti-fibrotic characteristics. They can induce cell proliferation, cell viability, migration, oogenesis, spermatogenesis, capacitation, acrosome reaction, and embryonic implantation. Exosomes have shown promising results in regenerative medicine such as liver fibrosis, stroke, cardiac ischemia, and skin injuries. Exosomes have been used to treat reproductive diseases such as erectile dysfunction and primary ovarian insufficiency. However, the study of exosomes in reproductive medicine is limited. In this article, we are going to review some of the researches on the use of stem cells and exosomes in reproductive medicine and suggest administration of a combination of exosomes for alleviating the symptoms of endometriosis and asthenozoospermia based on previous studies.     

外泌体介导的靶向基因运送及在心血管疾病中的应用

外泌体是体内几乎所有细胞分泌的具有双层脂质膜结构的纳米级小囊泡。外泌体大小均匀,平均直径为40～120 nm,存在于所有体液中。外泌体曾一度被认为是细胞成熟过程中清除废弃细胞器的‘垃圾袋’。但近年研究显示：外泌体含有丰富的来源于‘供体细胞’的信号分子,如蛋白质、DNA、mRNA、miRNA以及lncRNA等。当外泌体与‘受体细胞’融合时,这些信号分子便被运送到‘受体细胞’,从而实现细胞 细胞之间的通讯,影响‘受体细胞’的生理病理过程。虽然外泌体的研究目前主要集中在癌症等疾病的预防、诊断与治疗中,但是越来越多的研究显示,外泌体在心血管系统的生理及病理过程中同样发挥着重要作用。本文将对外泌体的起源、分离与纯化方法及外泌体介导的‘细胞 细胞’之间的通讯机制进行综述,并重点论述利用基因工程技术对外泌体进行靶向运输的方法及靶向外泌体运送在心血管疾病治疗中的应用。     

Exosomes surf on filopodia to enter cells at endocytic hot spots,traffic within endosomes,and are targeted to the ER

Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.