Faculty of Medicine, Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, Bialystok, Poland.
Department of Nephrology and Laboratory Medicine Faculty of Medicine Institute of Medical, Pharmaceutical and Health Sciences Graduate School of Medical Sciences, Kanazawa University, Toranomon Hospital, Nephrology Center, Tokyo, Japan.
Stem Cell Rev Rep. 2022 Mar;18(3):902-932. doi: 10.1007/s12015-021-10189-9. Epub 2021 Jun 10.
Extracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD.
基于细胞外囊泡 (EV) 的治疗方法被认为是一种很有前途的再生方法，这促使人们对 EV 在各种疾病中的作用进行了深入研究。在本研究中，我们对 EV 在慢性肾脏病 (CKD) 中的保护作用的现有实验证据进行了全面的系统评价。我们评估了基于 EV 的实验、EV 特征以及涉及 CKD 途径的效应分子。我们纳入了所有有肌酐或尿素数据的动物记录，并进行了分层单变量荟萃分析，以评估 EV 治疗效果的决定因素。我们确定了 35 项评估 EV 对肾脏保护作用的干预性研究，并根据它们对 CKD 机制的参与程度对其进行了分类。对这些研究的系统评估表明，EV 一致改善了不同 CKD 模型中的肾小球硬化、间质纤维化和细胞损伤。此外，EV 治疗可减缓 CKD 患者的肾功能下降进展。分层分析表明，疾病模型、给予的剂量和治疗干预的时间是治疗效果的潜在预测因素。总的来说，EV 治疗是实验研究中 CKD 进展的一种很有前途的方法。进一步规范 EV 方法、持续提高研究质量以及更好地了解 EV 有效性的决定因素，将有助于开展临床前研究，并可能有助于为 CKD 患者开展临床试验。
