Glutathione Peroxidase 3 Delivered by hiPSC-MSCs Ameliorated Hepatic IR Injury via Inhibition of Hepatic Senescence

Theranostics
Xiang QiKwan Man

Abstract

Background and Aims: Down-regulation of GPx3 accelerated hepatic senescence, which further caused overwhelming inflammation and severe liver graft injury. MSCs derived from human induced pluripotent stem cells (hiPSC-MSCs) have been developed as more efficient delivery vehicle with the property of injury tropism. Here, we aimed to explore the suppressive role of GPx3 in hepatic IR injury using novel delivery system of hiPSC-MSCs. Methods: The mice IR injury model with partial hepatectomy was established. The engineered hiPSC-MSCs delivering GPx3 was constructed. All the mice were segregated into three groups. hiPSC-MSC-GPx3, hiPSC-MSC-pCDH (vector control) or PBS were injected via portal vein after reperfusion. Liver injury was evaluated by histological and serological test. Hepatic apoptosis was detected by Tunel staining and remnant liver regeneration was assessed by Ki67 staining. The role of hepatic senescence in liver graft injury was evaluated in rat orthotopic liver transplantation model. The suppressive effect of GPx3 on hepatic senescence was examined in mice IR injury model and confirmed in vitro. Hepatic senescence was detected by SA-β-Gal and P16/ink4a staining. Results: GPx3 can be successfully delivered by hiPSC-M...Continue Reading

Citations

Apr 16, 2020·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Junbin ZhouXiao Xu
Sep 25, 2019·Cells·Irina V KholodenkoKonstantin N Yarygin
Jun 24, 2020·Journal of Translational Medicine·Man-Li ZhangJing Liu
Dec 6, 2018·Journal of Cellular Physiology·Yafan GongZiwei Zhang
Jul 8, 2020·International Journal of Molecular Sciences·Ehab Kotb ElmahallawyTokuma Yanai
Mar 31, 2021·Analytical Chemistry·Wen ZhangBo Tang

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Methods Mentioned

BETA
fluorescence-activated cell sorting
flow-cytometry
ELISA
flow cytometry
Profiler
PCR

Software Mentioned

SPSS

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