摘要
细胞外囊泡是由细胞主动分泌的具有磷脂双层膜结构的纳米级囊泡，广泛存在于体液中，是介导细胞间通讯的关键载体。根据其生物发生途径和尺寸，主要可分为外泌体、微囊泡和凋亡小体等亚型。外泌体起源于细胞内吞作用形成的多泡体，其生物发生受内体分选复合物等精密调控；微囊泡则主要通过质膜直接出芽产生。这些囊泡携带并传递丰富的生物活性分子，包括蛋白质、核酸和脂质，从而在生理和病理过程中发挥不可或缺的作用。在生理状态下，EVs参与免疫调节、组织稳态维持与再生修复。在病理过程中，它们则成为疾病发展的推手，如在肿瘤微环境重塑、转移前生态位形成、代谢紊乱、神经炎症及感染性疾病中扮演重要角色。基于其天然的递送特性和丰富的生物信息，EVs已成为极具潜力的疾病诊断生物标志物、预后评估工具以及新型药物递送系统。本文系统综述了细胞外囊泡的不同生物发生机制、其在多种生物学过程中的核心功能，并深入探讨了从分离表征到工程化应用的前沿进展，旨在为理解EVs的生物学意义及推动其临床转化提供全面视角。
关键词： 细胞外囊泡；外泌体；微囊泡；生物发生；细胞间通讯；疾病标志物；药物递送
Abstract
Extracellular vesicles (EVs) are nanoscale vesicles with a phospholipid bilayer membrane structure, actively secreted by cells, and widely present in body fluids, serving as key carriers for mediating intercellular communication. Based on their biogenesis pathways and sizes, they are primarily classified into subtypes such as exosomes, microparticles, and apoptotic bodies. Exosomes originate from multivesicular bodies formed by cellular endocytosis, with their biogenesis precisely regulated by mechanisms such as endosomal sorting complexes. Microparticles are mainly produced through direct budding from the plasma membrane. These vesicles carry and deliver a rich array of bioactive molecules, including proteins, nucleic acids, and lipids, playing an indispensable role in physiological and pathological processes. Under physiological conditions, EVs participate in immune regulation, tissue homeostasis maintenance, and regeneration and repair. In pathological processes, they act as facilitators of disease progression, playing important roles in tumor microenvironment remodeling, pre-metastatic niche formation, metabolic disorders, neuroinflammation, and infectious diseases. Due to their natural delivery properties and rich biological information, EVs have become highly promising disease biomarkers, prognostic assessment tools, and novel drug delivery systems. This article systematically reviews the different biogenesis mechanisms of EVs, their core functions in various biological processes, and explores cutting-edge advancements from isolation and characterization to engineering applications, aiming to provide a comprehensive perspective for understanding the biological significance of EVs and advancing their clinical translation.
Key words： Extracellular vesicles; Exosomes; Microparticles; Biogenesis; Intercellular communication; Disease biomarkers; Drug delivery
参考文献 References
[1] Li P ,Lu M ,Peng T , et al. An improvised one-step OptiPrep cushion ultracentrifugation method for outer membrane vesicles isolation of Klebsiella pneumoniae[J]. BMC Microbiology, 2024,24(1):548-548.
[2] Guo X ,Song J ,Liu M , et al. The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response.[J].Cancer biology & therapy, 2024, 25(1): 2356831-2356831.
[3] Contursi A ,Tacconelli S ,Berardino D S , et al. Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention[J].Frontiers in Pharmacology,2024,151520488-1520488.
[4] Zhang R ,Li G ,Wu Y , et al. Pathogenic mechanisms and potential applications of extracellular vesicles from periodontal pathogens in periodontitis[J].Frontiers in Immunology,2024,151513983-1513983.
[5] Sekar S ,Srikanth S ,Mukherjee G A , et al. Biogenesis and functional implications of extracellular vesicles in cancer metastasis[J].Clinical and Translational Oncology,2024, 27(7):1-23.
[6] Abida ,Alhuthali M H ,Alshehri M J , et al. Exosomes in infectious diseases: insights into leishmaniasis pathogenesis, immune modulation, and therapeutic potential[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2024,398(5):1-19.
[7] Deng R ,Cui X ,Zhang R , et al. Pathologic function and therapeutic potential of extracellular vesicle miRNA in sepsis[J].Frontiers in Pharmacology,2024,151452276-1452276.
[8] Vukelić I ,Šuša B ,Klobučar S , et al. Exosome-Derived microRNAs: Bridging the Gap Between Obesity and Type 2 Diabetes in Diagnosis and Treatment[J].Diabetology, 2024, 5(7):706-724.
[9] Punnachet T ,Chattipakorn C S ,Chattipakorn N , et al. Critical Role of Extracellular Vesicles in Diffuse Large B-Cell Lymphoma; Pathogenesis, Potential Biomarkers, and Targeted Therapy—A Narrative Review[J].Biomedicines, 2024,12(12):2822-2822.
[10] Su W ,Liao C ,Liu X . Angiogenic and neurogenic potential of dental-derived stem cells for functional pulp regeneration: A narrative review.[J].International endodontic journal, 2024,58(3):391-410.
[11] 胡清.细胞外囊泡miRNA-382-5p在创伤性脑损伤预后评估与靶向治疗中的作用及机制研究[D].中国人民解放军空军军医大学,2024.
[12] 英司奇.骨缺损动员肝细胞外囊泡调控H型血管促骨组织再生修复的作用机制研究[D].中国人民解放军空军军医大学,2024.
[13] 刘海啸,胡清,吴勋,等.细胞外囊泡运载的miRNA-382-5p介导星形胶质细胞-神经元信号交互加剧TBI后神经损伤[C]//中国医师协会,中国医师协会神经外科医师分会.第十八届中国医师协会神经外科医师年会摘要集-基础研究.第四军医大学唐都医院(唐都医院);,2024:215.
[14] 李莎莎,余飞,刘万卉. 细胞外囊泡表征检测方法的对比[J].中国生物化学与分子生物学报,2024,40(08):1093-1101.
[15] 赵亚婷.微流控芯片的功能化修饰及其在单细胞外囊泡研究中的应用[D].吉林大学,2024.
[16] 陆滢.三角褐指藻细胞外囊泡保护皮肤氧化应激损伤的作用研究[D].浙江大学,2024.
[17] 居裔昆.负载纳米酶及细胞外囊泡的自修复水凝胶促进皮瓣存活的研究[D].中南大学,2024.
[18] 申干.搭载内质网的工程化细胞外囊泡调节细胞应激水平的实验研究[D].中国人民解放军海军军医大学,2024.
[19] 高立烊.水凝胶微液滴技术在单细胞外囊泡DNA分析中的应用[D].山东大学,2024.
[20] 易小梅.SLC1A5阳性的小细胞外囊泡促进结直肠癌细胞增殖、迁移和侵袭[D].赣南医科大学,2024.
[21] 肖雨尘.小细胞外囊泡在心力衰竭中的作用研究[D].中国人民解放军海军军医大学,2024.
[22] 冉柳毅.细胞外囊泡miRNA基因作为青少年抑郁诊断标志物和干预靶标的筛查及验证研究[D].重庆医科大学,2024.
[23] 李悦含.输卵管细胞外囊泡对早期胚胎发育的影响及其机制研究[D].华中科技大学,2024.
[24] 付菲.乳牙牙髓干细胞外囊泡调控中性粒细胞免疫功能缓解牙髓炎症的作用机制研究[D].中国人民解放军空军军医大学,2024.
[25] 徐放.基于磷脂探针修饰的ZIF-8材料用于细胞外囊泡的分离富集及应用研究[D].苏州大学,2024.
[26] 马晟.一、MFSD2A在肝细胞肝癌组织中的表达情况及临床意义 二、基于机器学习建立肺鳞癌血浆细胞外囊泡蛋白标志物的诊断和预后模型[D].北京协和医学院,2024.
[27] 刘夺,刘培源,李连月,等. 工程化细胞外囊泡的设计合成与生物医学应用[J].合成生物学,2024,5(01):154-173.
[28] 王珊,曹玉林,吴迪,等. 细胞外囊泡表面蛋白冠的研究进展[J].中国生物工程杂志,2024,44(Z1):134-141.
[29] 徐文文.细胞外囊泡LINC00482促进肺癌脑转移的作用及机制研究[D].东南大学,2023.
[30] 龙宜,杨佳明,叶花,等. 细胞外囊泡在少肌性肥胖中的作用及机制[J].中国组织工程研究,2024,28(02):315-320.