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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Med. | doi: 10.3389/fmed.2019.00269

Exosomes from mesenchymal stem cells alleviate ischemic- reperfusion injury in kidney transplantation through inhibition of inflammation and apoptosis

 Long Li1, 2, 3, Rulin Wang4,  Yichen Jia5, 6,  Ruiming Rong5, 6, Tongyu Zhu5, 6* and Ming Xu5, 6*
  • 1Department of Urology, Zhongshan Hospital, Fudan University, China
  • 2Shanghai Key Laboratory of Organ Transplantation, China
  • 3Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, China
  • 4Department of Urology, First Affiliated Hospital of Zhengzhou University, China
  • 5Department of Urology Surgery, Zhongshan Hospital, Fudan University, China
  • 6Shanghai Key Laboratory of Organ Transplantation, China

The renoprotection of mesenchymal stem cells (MSC) following kidney ischemia reperfusion injury (IRI) have been reported recently, thus the present study aimed to investigate the protective mechanism of MSCs in a rat IRI model. Rats were divided into five groups according to the different treatments: sham group, IRI group, MSC group, MSC-ex group and MSC-ex+RNAase group, and kidney function, pathological conditions, proinflammatory cytokines, transcription factors and cell apoptosis were assessed. The results revealed that MSCs and exosomes from MSCs reduced the levels of Scr and BUN, suggesting a renoprotective effect in IRI. In addition, the expression of pNF-κB and pIκB was decreased in the MSC and MSC-ex groups, but total IκB expression was increased. As for apoptosis, MSC and exosomes both reduced the expression of caspase-9, cleaved caspase-3 and Bax, and increased the levels of Bcl-2, confirming the anti-apoptotic function in a rat renal IRI model. However, based on our findings, the MSC-ex+RNAase group shared the same features as the IRI group, likely due to the ability of RNA hydrolase to eliminate the function of exosomes. Mechanistically, exosomes originating from MSCs have protective functions in IRI via downregulation of the level of apoptotic and inflammatory response, in which the NF-κB signaling pathway plays a key role, suggesting a new mechanism for the renal protection of MSCs.

Keywords: Mesenchymal Stem Cells, Exosomes, ischemic-reperfusion injury, Inflammation, Apoptosis

Received: 18 Aug 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 Li, Wang, Jia, Rong, Zhu and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Tongyu Zhu, Department of Urology Surgery, Zhongshan Hospital, Fudan University, Shanghai, China, zs_tyzhu@163.com
Mx. Ming Xu, Department of Urology Surgery, Zhongshan Hospital, Fudan University, Shanghai, China, xu.ming@zs-hospital.sh.cn