Author/Authors :
Tang, Yunxia Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Li, Qiongshu Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Meng, Fanwei Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Huang, Xingyu Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Li, Chan Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Zhou, Xin Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Zeng, Xiaoping Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , He, Yixin Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Liu, Jia Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Hu, Xiang Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China , Hu, Ji-Fan 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 , Li, Tao Shenzhen Beike Cell Engineering Research Institute - Yuanxing Science and Technology Building - Nanshan, Shenzhen 518057, China
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.
Keywords :
Therapeutic Potential , HGF-Expressing Human , Human umbilical Cord , Mesenchymal Stem Cells , Mice , Acute Liver Failure
