Street J M, Koritzinsky E H, Glispie D M, Star R A, Yuen P S T
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Adv Clin Chem. 2017;78:103-122. doi: 10.1016/bs.acc.2016.07.003. Epub 2016 Aug 18.
Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies.
外泌体由大多数细胞释放,可从包括尿液在内的所有生物流体中分离出来。外泌体是作为内体途径的一部分形成的小囊泡,其包含被脂质双层包围的细胞物质,该脂质双层可追溯到质膜。与未分级的尿液相比,外泌体可能是用于生物标志物发现的更具针对性的物质来源,并且无需进行侵入性组织活检即可提供诊断和病理生理信息。包括蛋白质、mRNA、miRNA和脂质在内的细胞质成分均已在外泌体组分中进行了研究。对于多种肾脏或泌尿生殖道疾病,已经成功鉴定出许多前瞻性尿液外泌体生物标志物;检测全身性疾病也可能实现。外泌体的分离和分析可以通过几种方法实现,尽管许多方法需要专门的设备或涉及冗长的方案。临床环境中对及时分析的需求推动了大量创新,最近出现了几种有前景的选择。对外泌体分离、表征和标准化程序达成共识将解决现有候选外泌体生物标志物的关键临床转化瓶颈,并为更多的发现研究提供模板。