Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, People's Republic of China.
Stem Cell Res Ther. 2019 Apr 17;10(1):119. doi: 10.1186/s13287-019-1227-8.
Stem cell-based therapy appears to be a promising new candidate for acute kidney injury (AKI) management. Traditionally, it has been accepted that the mechanism underlying the regenerative effect of stem cells is based on their paracrine/endocrine activity, including release of bioactive factors that act on injured renal cells and presentation of proangiogenic, antiapoptotic, antioxidative, and immunomodulatory effects. Recently, multiple studies have confirmed that extracellular vesicles (EVs) are a kind of vesicle rich in a broad variety of biologically active molecules, including lipids, proteins, and, in particular, nucleic acids. EVs are able to transfer genetic information to target cells, alter target gene regulatory networks, and exert biological effects. Stem cell-derived EVs (SC-EVs) are emerging as potent genetic information sources that deliver mRNAs and miRNAs to injured renal cells and exert renoprotective effects during AKI. On the other hand, EVs originating from injured renal cells also contain genetic information that is believed to be able to influence phenotypic and functional changes in stem cells, favoring renal recovery. In this review, we summarize studies providing evidence of genetic communication during the application of stem cells in preclinical AKI models, aiming to clarify the mechanism and describe the therapeutic effects of stem cell-based therapy in AKI patients.
基于干细胞的疗法似乎是急性肾损伤 (AKI) 治疗的一种有前途的新候选方法。传统上,人们普遍认为干细胞再生作用的机制基于其旁分泌/内分泌活性,包括释放作用于受损肾细胞的生物活性因子,并表现出促血管生成、抗凋亡、抗氧化和免疫调节作用。最近,多项研究证实,细胞外囊泡 (EVs) 是一种富含多种生物活性分子的囊泡,包括脂质、蛋白质,特别是核酸。EVs 能够将遗传信息传递给靶细胞,改变靶基因调控网络,并发挥生物学作用。干细胞来源的 EVs (SC-EVs) 作为潜在的遗传信息源,可将 mRNA 和 miRNA 传递给受损的肾细胞,并在 AKI 期间发挥肾保护作用。另一方面,源自受损肾细胞的 EVs 也含有遗传信息,据信能够影响干细胞的表型和功能变化,有利于肾脏恢复。在这篇综述中,我们总结了提供证据证明在临床前 AKI 模型中应用干细胞时遗传通讯的研究,旨在阐明机制并描述 AKI 患者基于干细胞的治疗的治疗效果。