Journal
MOLECULAR THERAPY
Volume 25, Issue 2, Pages 465-479Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2016.11.019
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Funding
- National Natural Science Foundation of China [81200312, 81670549, 81670502]
- China Postdoctoral Science Foundation [2015M580403, 2016T90431]
- Natural Science Foundation of Jiangsu Province [BE2016717, BK2012288]
- Scientific Research Foundation of Jiangsu University [11JDG062]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Young Backbone Teacher Training Project of Jiangsu University
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Exosomes are small biological membrane vesicles secreted by various cells, including mesenchymal stem cells (MSCs). We previously reported that MSC-derived exosomes (MSC-Ex) can elicit hepatoprotective effects against toxicant-induced injury. However, the success of MSC-Ex-based therapy for treatment of liver diseases and the underlying mechanisms have not been well characterized. We used human umbilical cord MSC-derived exosome (hucMSC-Ex) administrated by tail vein or oral gavage at different doses and, in engrafted liver mouse models, noted antioxidant and anti-apoptotic effects and rescue from liver failure. A single systemic administration of hucMSC-Ex (16 mg/ kg) effectively rescued the recipient mice from carbon tetrachloride (CCl4)-induced liver failure. Moreover, hucMSC-Ex-derived glutathione peroxidase1 (GPX1), which detoxifies CCl4 and H2O2, reduced oxidative stress and apoptosis. Knockdown of GPX1 in hucMSCs abrogated antioxidant and anti-apoptotic abilities of hucMSC-Ex and diminished the hepatoprotective effects of hucMSC-Ex in vitro and in vivo. Thus, hucMSC-Ex promote the recovery of hepatic oxidant injury through the delivery of GPX1.
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