title: Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure.
abstract: Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms.
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Qiongshu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Fanwei
authors.initials: F
authors.lastname: Meng
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Li
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: He
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin University, Changchun 130012, China; Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304, USA.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen 518057, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li