{"title":"Systems Approaches to Cell Culture-Derived Extracellular Vesicles for Acute Kidney Injury Therapy: Prospects And Challenges","authors":"David J. Lundy, Barbara Szomolay, Chia-Te Liao","doi":"10.1093/function/zqae012","DOIUrl":null,"url":null,"abstract":"\n Acute kidney injury (AKI) is a heterogeneous syndrome, comprising diverse aetiologies of kidney insults which result in high mortality and morbidity if not well-managed. Although great efforts have been made to investigate underlying pathogenic mechanisms of AKI, there are limited therapeutic strategies available. Extracellular vesicles (EV) are membrane-bound vesicles secreted by various cell types which can serve as cell-free therapy through transfer of bioactive molecules. In this review, we first overview the AKI syndrome and EV biology, with a particular focus on the technical aspects and therapeutic application of cell culture-derived EVs. Secondly, we illustrate how multi-omic approaches to EV miRNA, protein and genomic cargo analysis can yield new insights into their mechanisms of action and address unresolved questions in the field. We then summarise major experimental evidence regarding the therapeutic potential of EVs in AKI, which we subdivide into stem cell and non-stem cell-derived EVs. Finally, we highlight the challenges and opportunities related to clinical translation of animal studies into human patients.","PeriodicalId":503843,"journal":{"name":"Function","volume":"105 17","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Function","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/function/zqae012","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Acute kidney injury (AKI) is a heterogeneous syndrome, comprising diverse aetiologies of kidney insults which result in high mortality and morbidity if not well-managed. Although great efforts have been made to investigate underlying pathogenic mechanisms of AKI, there are limited therapeutic strategies available. Extracellular vesicles (EV) are membrane-bound vesicles secreted by various cell types which can serve as cell-free therapy through transfer of bioactive molecules. In this review, we first overview the AKI syndrome and EV biology, with a particular focus on the technical aspects and therapeutic application of cell culture-derived EVs. Secondly, we illustrate how multi-omic approaches to EV miRNA, protein and genomic cargo analysis can yield new insights into their mechanisms of action and address unresolved questions in the field. We then summarise major experimental evidence regarding the therapeutic potential of EVs in AKI, which we subdivide into stem cell and non-stem cell-derived EVs. Finally, we highlight the challenges and opportunities related to clinical translation of animal studies into human patients.
急性肾损伤(AKI)是一种异质性综合征,由多种病因引起的肾脏损伤组成,如果处理不当,死亡率和发病率都很高。尽管人们一直在努力研究 AKI 的潜在致病机制,但可用的治疗策略却很有限。细胞外囊泡(EV)是由各种细胞分泌的膜结合囊泡,可通过转移生物活性分子作为无细胞疗法。在这篇综述中,我们首先概述了 AKI 综合征和 EV 生物学,尤其侧重于细胞培养衍生 EV 的技术方面和治疗应用。其次,我们说明了用多组学方法对 EV 的 miRNA、蛋白质和基因组货物进行分析如何能对其作用机制产生新的认识,并解决该领域尚未解决的问题。然后,我们总结了EVs在AKI中治疗潜力的主要实验证据,并将其细分为干细胞和非干细胞衍生的EVs。最后,我们强调了将动物研究临床转化为人类患者所面临的挑战和机遇。