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。     

间充质干细胞外泌体中的RNA与蛋白质

间充质干细胞(mesenchymal stem cell,MSC)外泌体是MSC中的多泡小体与细胞膜融合时分泌到细胞外环境中的50～200 nm大小的细胞外囊泡。MSC外泌体含有TSG101、CD9和CD81等典型蛋白质与多种RNA。人们逐渐认识到外泌体是通过传递其蛋白质和RNA等内容物到受体细胞发挥作用的。因此,MSC外泌体的治疗潜能可能是因为它含有特殊的蛋白质或RNA。该文对外泌体蛋白质和RNA的作用机制进行探究,并提出MSC外泌体很可能通过蛋白质而不是RNA发挥效应。     

外泌体与乳腺癌关系的研究进展

外泌体是细胞经过"内吞-融合-外排"等一系列调控过程而形成的细胞外纳米级小囊泡。外泌体通过其携带的蛋白或RNA影响受体基因调控网络或表观遗传重组,进而调控细胞的生理过程。研究表明,乳腺癌细胞自身分泌的外泌体和外界细胞分泌的外泌体在乳腺癌发生、发展过程中的细胞迁移、细胞分化和免疫应答等方面发挥重要作用。本文对外泌体与乳腺癌关系的研究进展进行综述。     

间充质干细胞来源外泌体在骨关节炎治疗中的作用

骨关节炎(OA)是最常见的慢性退行性骨关节疾病,目前对骨关节炎的治疗还没有特效疗法。间充质干细胞(MSC)对软骨修复有较好的疗效,间充质干细胞来源外泌体可能在这一治疗过程中发挥重要作用。外泌体是细胞间的通讯载体,能在细胞间传递生物活性脂质、核酸以及蛋白质等生物活性分子对骨关节炎产生一定影响。本文就探讨间充质干细胞来源的外泌体治疗骨关节炎过程中的作用机制与可行性做出综述。     

间充质干细胞来源的外泌体治疗炎症性肠病研究进展*

间充质干细胞主要通过免疫调控和旁分泌在炎症性疾病的治疗中发挥功能。MSC的旁分泌效应是通过分泌可溶性因子并释放外泌体而发挥作用。外泌体将DNA、蛋白质/肽、mRNA、microRNA、脂质和细胞器等成分转移到受体细胞中直接发挥功能。MSC-Exo替代MSC为炎症性肠病的治疗提供了一种新策略。总结不同组织(骨髓、脐带和脂肪)来源的MSC- Exo用于治疗炎症性肠病的研究进展。     

外泌体源性蛋白对缺血性脑卒中的作用

缺血性脑卒中严重危害人类健康和生活质量,探寻其发病机制和保护策略一直是脑血管研究领域的重点问题。外泌体作为细胞主动分泌的纳米级囊泡,通过携带丰富的蛋白质、DNA、miRNA等生物大分子,在胞间的物质运输和信息交换中发挥重要作用。研究表明,中枢外泌体在缺血性脑卒中的发病及后期的修复的病理生理过程中均发挥了重要的作用。外泌体源性蛋白作为外泌体的重要组成部分,参与了缺血性脑卒中的发生和发展。本文就外泌体源性蛋白质的生物学特性及其在缺血性脑卒中的作用和机制研究进行综述。     

血管内皮细胞外泌体的生物学作用及其分子机制的研究进展

外泌体是细胞分泌的一种纳米级胞外囊泡,通过携带蛋白质和核酸等小分子物质参与细胞间信号交流。内皮细胞来源的外泌体在许多病理生理过程中起着十分重要的作用。现综述血管内皮细胞外泌体的生物学作用及其分子机制的最新研究进展,重点关注血管内皮细胞外泌体在心血管疾病、缺血再灌注损伤、肿瘤发生发展和免疫调节等过程中的重要作用,及其调控受体细胞功能的分子机制。     

干细胞来源外泌体在心肌损伤修复中的作用

目前普遍认为干细胞在心肌损伤修复中的旁分泌作用是其发挥疗效的重要途径之一。外泌体是旁分泌的重要介质,是由细胞分泌的具有磷脂双分子层结构的囊性小泡,可以转运蛋白质、脂质和核酸分子到受体细胞,介导生理和病理条件下细胞间通讯。多种干细胞,包括胚胎干细胞、诱导多能干细胞、心脏祖细胞、间充质干细胞和心肌球细胞等来源的外泌体对受损心脏的保护作用已被广泛证实,其在心肌损伤修复中的治疗效果备受关注。本综述总结了目前关于不同干细胞来源的外泌体在心肌损伤修复研究中的最新进展,包括治疗潜力和作用机制。     

MSC来源的外泌体在OA中潜在的免疫调节及抗炎作用

骨性关节炎(osteoarthritis, OA)是一种整体的"器官"疾病,伴随着复杂的病理改变。大量研究表明, OA中存在一种慢性、轻度的炎症,伴随相关免疫反应,并作为中心环节贯穿其病理变化过程。间充质干细胞(mesenchymal stem cell, MSC)因其抗炎免疫调节的能力而备受关注。间充质干细胞经旁分泌途径分泌外泌体(exosomes),是其发挥抗炎及免疫调节作用的主要机制之一。MSC来源的外泌体介导传递具有抗炎及免疫活性的分子,尤其是miRNA,协调炎症微环境并促进组织修复重建。该文就MSC来源外泌体在OA中潜在的免疫调节、抗炎作用及其可塑性进行探讨,以期为OA的治疗提供新思路。     

外泌体在糖尿病及其并发症的发生、发展和诊治中的作用

外泌体是一种纳米级大小,由细胞主动吞吐而分泌的具有膜结构的细胞外囊泡样小体,可以携带和转移很多生物分子,如DNA片段、环状RNA (circ RNA)、m RNA、微小RNA (mi RNA)、功能蛋白、转录因子等,从而成为细胞间信息传递的载体。近年来外泌体与糖尿病的关系受到广泛关注,它们在胰岛素敏感性、葡萄糖稳态、血管内皮功能等方面发挥重要作用。本文综述外泌体参与糖尿病及其并发症的病理生理过程,并探讨了外泌体作为糖尿病治疗的靶点及其在糖尿病的诊断与治疗中的作用和前景。     

Multifunctional role of microRNAs in mesenchymal stem cell-derived exosomes in treatment of diseases

Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases, injury repair, degenerative diseases, and tumors. Exosomes are small vesicles rich in a variety of nucleic acids [including messenger RNA, Long non-coding RNA, microRNA (miRNA), and circular RNA], proteins, and lipids. Exosomes can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between cells. Like exosomes, miRNAs were neglected before their role in various activities of organisms was discovered. Several studies have confirmed that miRNAs play a vital role within exosomes. This review focuses on the specific role of miRNAs in MSC-derived exosomes (MSC-exosomes) and the methods commonly used by researchers to study miRNAs in exosomes. Taken together, miRNAs from MSC-exosomes display immense potential and practical value, both in basic medicine and future clinical applications, in treating several diseases.     

Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer

Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.     

脂肪间充质干细胞来源外泌体的功能

外泌体是细胞外膜质纳米囊泡,将蛋白质、核酸(DNA和RNA)转运到靶细胞中,介导局部和系统的细胞间通信,从而改变受体细胞的行为.这些小泡在许多生物功能中发挥重要作用,如脂肪合成、免疫调节、神经再生和肿瘤调节等.脂肪间充质干细胞目前被认为是细胞治疗和再生医学领域中一种功能丰富的工具,可产生和分泌多种外泌体,继承细胞的多种...     

Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration

Poor healing of cutaneous wounds is a common medical problem in the field of traumatology. Due to the intricate pathophysiological processes of wound healing, the use of conventional treatment methods, such as chemical molecule drugs and traditional dressings, have been unable to achieve satisfactory outcomes. Within recent years, explicit evidence suggests that mesenchymal stem cells (MSCs) have great therapeutic potentials on skin wound healing and regeneration. However, the direct application of MSCs still faces many challenges and difficulties. Intriguingly, exosomes as cell-secreted granular vesicles with a lipid bilayer membrane structure and containing specific components from the source cells may emerge to be excellent substitutes for MSCs. Exosomes derived from MSCs (MSC-exosomes) have been demonstrated to be beneficial for cutaneous wound healing and accelerate the process through a variety of mechanisms. These mechanisms include alleviating inflammation, promoting vascularization, and promoting proliferation and migration of epithelial cells and fibroblasts. Therefore, the application of MSC-exosomes may be a promising alternative to cell therapy in the treatment of cutaneous wounds and could promote wound healing through multiple mechanisms simultaneously. This review will provide an overview of the role and the mechanisms of MSC-derived exosomes in cutaneous wound healing, and elaborate the potentials and future perspectives of MSC-exosomes application in clinical practice.     

Advances on liver cell-derived exosomes in liver diseases

Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, which contain several donor cell-associated proteins as well as mRNA, miRNA, and lipids and coordinate multiple physiological and pathological functions through horizontal communication between cells. Almost all types of liver cells, such as hepatocytes and Kupffer cells, are exosome-releasing and/or exosome-targeted cells. Exosomes secreted by liver cells play an important role in regulating general physiological functions and also participate in the onset and development of liver diseases, including liver cancer, liver injury, liver fibrosis and viral hepatitis. Liver cell-derived exosomes carry liver cell-specific proteins and miRNAs, which can be used as diagnostic biomarkers and treatment targets of liver disease. This review discusses the functions of exosomes derived from different liver cells and provides novel insights based on the latest developments regarding the roles of exosomes in the diagnosis and treatment of liver diseases.     

外泌体在免疫调控及肿瘤发生中的功能

已知细胞间的信息交流不仅可以通过直接接触,或释放信号分子等方式,同时还存在另一种细胞通讯方式即释放外泌体。外泌体是由细胞分泌,直径为30～100 nm的囊泡结构。外泌体含有蛋白质、脂质、mRNAs和miRNAs等成分,并且能够靶向运输到其他细胞或组织中,从而在细胞间的信息交流、物质传递方面发挥重要作用。本文对外泌体的基本特征、形成过程、功能以及在疾病诊断与治疗中的应用等方面进行简要综述,重点介绍外泌体在免疫调控和肿瘤发生方面的功能。外泌体作为一种广泛存在的亚细胞成分,虽然体积小,组成成分简单,然而,其复杂功能具有重要的研究价值。对外泌体功能的深入了解将为肿瘤等疾病的预防和治疗提供更多的诊断标志物、疫苗以及治疗思路与手段。     

Physiological and pathological impact of exosomes of adipose tissue

Exosomes are nanovesicles that have emerged as a new intercellular communication system for transporting proteins and RNAs; recent studies have shown that they play a role in many physiological and pathological processes such as immune regulation, cell differentiation, infection and cancer. By transferring proteins, mRNAs and microRNAs, exosomes act as information vehicles that alter the behavior of recipient cells. Compared to direct cell‐cell contact or secreted factors, exosomes can affect recipient cells in more efficient ways. In whole adipose tissues, it has been shown that exosomes exist in supernatants of adipocytes and adipose stromal cells (ADSCs). Adipocyte exosomes are linked to lipid metabolism and obesity‐related insulin resistance and exosomes secreted by ADSCs are involved in angiogenesis, immunomodulation and tumor development. This review introduces characteristics of exosomes in adipose tissue, summarizes their functions in different physiological and pathological processes and provides the further insight into potential application of exosomes to disease diagnosis and treatment.     

Exosome secretion: molecular mechanisms and roles in immune responses

Exosomes are small membrane vesicles, secreted by most cell types from multivesicular endosomes, and thought to play important roles in intercellular communications. Initially described in 1983, as specifically secreted by reticulocytes, exosomes became of interest for immunologists in 1996, when they were proposed to play a role in antigen presentation. More recently, the finding that exosomes carry genetic materials, mRNA and miRNA, has been a major breakthrough in the field, unveiling their capacity to vehicle genetic messages. It is now clear that not only immune cells but probably all cell types are able to secrete exosomes: their range of possible functions expands well beyond immunology to neurobiology, stem cell and tumor biology, and their use in clinical applications as biomarkers or as therapeutic tools is an extensive area of research. Despite intensive efforts to understand their functions, two issues remain to be solved in the future: (i) what are the physiological function(s) of exosomes in vivo and (ii) what are the relative contributions of exosomes and of other secreted membrane vesicles in these proposed functions? Here, we will focus on the current ideas on exosomes and immune responses, but also on their mechanisms of secretion and the use of this knowledge to elucidate the latter issue.     

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.     

Exosomes: New players in cell-cell communication

Exosomes are small membrane vesicles of endosomal origin, which are secreted from a variety of cell types. During the 1980s exosomes were first described as organelles to remove cell debris and unwanted molecules. The discovery that exosomes contain proteins, messenger and microRNAs suggests a role as mediators in cell-to-cell communication. Exosomes can be transported between different cells and influence physiological pathways in the recipient cells. In the present review, we will summarize the biological function of exosomes and their involvement in physiological and pathological processes. Moreover, the potential clinical application of exosomes as biomarkers and therapeutic tools will be discussed.