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Kidney Week

Abstract: PO0984

Mesenchymal Stem Cell Exosomes Protect Mouse Peritoneal Injury Induced by Human Peritonitis Dialysis Effluent

Session Information

  • Peritoneal Dialysis
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 702 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Yu, Fang, Army Military Medical University, Daping Hospital,Department of Nephrology, Chongqing, China
  • Chen, Kehong, Army Military Medical University, Daping Hospital,Department of Nephrology, Chongqing, China
  • Chen, Jia, Army Military Medical University, Daping Hospital,Department of Nephrology, Chongqing, China
  • He, Yani, Army Military Medical University, Daping Hospital,Department of Nephrology, Chongqing, China
Background

Peritoneal fibrosis is a severe complication of peritoneal dialysis, but there are few effective therapies for it. The purpose of this study was to investigate the protective effect of exosomes secreted by mouse bone marrow mesenchymal stem cells(MSC) on peritoneal injury and to reveal the mechanism.

Methods

Forty-two male C57BL/6 mice were randomly divided into a normal group, a control group (2.5% glucose dialysate), a peritonitis-effluent group (The overnight 2.5% glucose dialysate of patients with peritonitis), a high glucose(4.25%) dialysate group, a peritonitis-dialysate+exosome group, and a high glucose dialysate+exosome group. The mouse model of peritoneal injury was constructed by intraperitoneal injection of human peritonitis dialysis effluent continuously for 42 days. The mice in the exosome treatment group received intraperitoneal injection of MSC-exosomes twice. The level of peritoneal structural and functional damage was detected. The effect of MSC-exosomes was validated in vitro.

Results

Peritoneal transport and structure was significantly impaired in the peritonitis-effluent group and the high glucose dialysate group after 42 days, and was significantly higher than control group. The results suggested that human peritonitis dialysis effluent could be used to construct a mouse model of peritoneal injury. Masson staining showed that fibrosis degree of exosome treatment group was significantly less than peritonitis-effluent group. Immunohistochemical analysis showed that expressions of mesothelial markers E-cadherin and ZO-1, neutrophil granulocytes (MPO) and macrophages (F4/80), and fibrosis markers(collagen I,a-SMA) in exosome treatment group were significantly lower than peritonitis-effluent group. Peritoneal ultrafiltration function of exosome treatment group was significantly improved than peritonitis-effluent group. In vitro experiments showed that exosomes could down-regulate the secretion of IL-1β, IL-6 and TGF-β1 by peritoneal mesothelial cells stimulated by high glucose dialysate, maintain expression of mesothelial cell marker (E-cadherin), and inhibit mesenchymal marker (a-SMA), suggesting that exosomes could inhibit the transdifferentiation of peritoneal mesenchymal cell-mesenchymal cells (MMT).

Conclusion

MSC-exosomes can alleviate peritoneal fibrosis by inhibiting peritoneal mesothelial cell-mesenchymal cell transdifferentiation.