title: NK Cell Regulatory Property is Involved in the Protective Role of MSC-Derived Extracellular Vesicles in Renal Ischemic Reperfusion Injury.
abstract: Immunomodulation has been regarded as an important therapeutic aspect of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in renal ischemic reperfusion injury (IRI), and the specific mechanism still unclear. Here, we attempt to test the function of human MSC-EVs on renal IRI by targeting the natural killer (NK) cells and to investigate the possible mechanism. Data indicated that EVs decreased NK cells in spleen and ischemic kidney. Both the EVs and antibody-dependent depletion of NK cells displayed a protective role in IRI rats. Moreover, the splenectomy model was established to evaluate the role of spleen in this process. It showed that the NK cell regulatory ability and renal protective effects by EVs still exist without spleen, which is unlike MSC properties published previously. Further, the down-regulation of chemokines in injured kidney and the delivery of RNAs through EVs in vitro were also observed. Through the microRNA array test, various inflammation-related microRNAs highly expressed in MSC-EVs compared with fibroblast EVs were tested. Thus, these results indicated that MSC-EVs could ameliorate renal ischemic reperfusion injury by decreasing NK cells and the spleen is not necessary in this process. The regulation of chemokines in injured kidney was the other factor, and the transfer of various microRNAs in the MSC-EVs may be involved. This provides direction for future clinical applications.
authors: 1 Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China.
authors: Xiangyu
authors: X
authors: Zou
authors: 1 Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China.
authors: Di
authors: D
authors: Gu
authors: 1 Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China.|2 Department of Urology, Affiliated Zhongda Hospital of Southeast University , Nanjing, China.
authors: Guangyuan
authors: G
authors: Zhang
authors: 3 Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University , Shanghai, China.
authors: Liang
authors: L
authors: Zhong
authors: 4 Department of Urology, Ningbo No. 2 Hospital , Ningbo, China .
authors: Zhongliang
authors: Z
authors: Cheng
authors: 1 Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China.
authors: Guohua
authors: G
authors: Liu
authors: 1 Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China.
authors: Yingjian
authors: Y
authors: Zhu
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D000067128:Extracellular Vesicles / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology / Q000628:therapy*
chemical_list: D035683:MicroRNAs
keywords: NK cell; extracellular vesicles; mesenchymal stromal cell; renal ischemic reperfusion injury; spleen