Liao Chunling, Chen Guangyong, Yang Qian, Liu Yiping, Zhou Tianbiao
Department of Nephrology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
Front Cell Dev Biol. 2022 Mar 11;10:824752. doi: 10.3389/fcell.2022.824752. eCollection 2022.
Renal fibrosis (RF) is central pathological pathway for kidney diseases, with the main pathological features being the aberrant accumulation of myofibroblasts that produce accumulation of extracellular matrix in the renal interstitium and glomeruli. Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with RF. Current treatment strategies for RF are ineffective. Mesenchymal stem cells (MSCs) have been found to be able to treat organ fibrosis including RF, but they have some safety problems, such as cell rejection, carcinogenicity, and virus contamination, which limit the application of MSCs. However, current studies have found that MSCs may exert their therapeutic effect by releasing extracellular vesicles (EVs). MSC-EVs can transfer functional proteins and genetic material directly to the recipient cells. As non-cell membrane structures, MSC-EVs have the advantages of low immunogenicity, easy preservation, and artificial modification, but do not have the characteristics of self-replication and ectopic differentiation. Therefore, EVs are safer than MSCs for treatment, but might be less effective than MSCs. Recent studies have also found that MSC-EVs can improve renal function and pathological changes of RF. Thus, this review summarizes the therapeutic effect of MSC-EVs on RF and the mechanisms that have been discovered so far, so as to provide a theoretical basis for the further study of the role of MSC-EVs in treating RF diseases.
肾纤维化(RF)是肾脏疾病的核心病理途径,其主要病理特征是肌成纤维细胞异常积聚,导致肾间质和肾小球中细胞外基质堆积。急性肾损伤(AKI)和慢性肾脏病(CKD)均与RF相关。目前针对RF的治疗策略效果不佳。已发现间充质干细胞(MSCs)能够治疗包括RF在内的器官纤维化,但存在一些安全问题,如细胞排斥、致癌性和病毒污染等,这限制了MSCs的应用。然而,目前研究发现MSCs可能通过释放细胞外囊泡(EVs)发挥治疗作用。MSC-EVs可将功能蛋白和遗传物质直接传递给受体细胞。作为非细胞膜结构,MSC-EVs具有免疫原性低、易于保存和可人工修饰等优点,但不具备自我复制和异位分化的特性。因此,EVs在治疗方面比MSCs更安全,但可能不如MSCs有效。近期研究还发现,MSC-EVs可改善RF的肾功能和病理变化。因此,本综述总结了MSC-EVs对RF的治疗作用及目前已发现的机制,为进一步研究MSC-EVs在治疗RF疾病中的作用提供理论依据。