Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure

被引:56
作者
Liu, Zongcai [1 ]
Meng, Fanwei [1 ]
Li, Chan [1 ]
Zhou, Xin [1 ]
Zeng, Xiaoping [1 ]
He, Yixin [1 ]
Mrsny, Randall J. [3 ,4 ]
Liu, Muyun [1 ]
Hu, Xiang [1 ]
Hu, Ji-Fan [2 ,3 ]
Li, Tao [1 ]
机构
[1] Shenzhen Beike Cell Engn Res Inst, Shenzhen, Guangdong, Peoples R China
[2] Stanford Univ, Sch Med, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA
[3] GMR Epigenet, Palo Alto, CA USA
[4] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England
基金
美国国家卫生研究院;
关键词
acute liver failure; anti-inflammation; antioxidants; apoptosis; hepatic regeneration; umbilical cord mesenchymal stromal cells; HEPATOCYTE GROWTH-FACTOR; STEM-CELLS; IN-VITRO; HEPATIC-FAILURE; MARROW; TRANSPLANTATION; REGENERATION; INJURY; ADULT; DIFFERENTIATION;
D O I
10.1016/j.jcyt.2014.05.018
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background aims. Acute liver failure (ALP), a life-threatening disease characterized by the sudden loss of hepatic function, can occur after an accidental or intentional acetaminophen overdose. Methods. With, the use of an ALP mouse model, we examined both the preventive and therapeutic potential of intravenously administered human umbilical cord derived mesenchymal stromal cells (hUCMSCs). Primary hUCMSCs were purified from freshly collected full-term umbilical cords and intravenously transplanted into BALB/c mice either before and after ALP induced by acetaminophen intoxication. We found that hUCMSCs significantly improved survival rates and relative liver weight of mice in both pre-ALF and post-ALP animals. Correspondingly, serum levels of markers that reflect hepatic injury (ie, aspartate aminotransferase, alanine aminotransferase and total bilirubin) were significantly attenuated in the group receiving hUCMSC therapy. Results. Mechanistically, we found that the protective potential of intravenously administered hUCMSCs was mediated by paracrine pathways that involved antioxidants (glutathione, superoxide dismutase), the reduction of inflammatory agents (tumor necrosis factor-a, interleukin-6) and elevated serum levels of hepatocyte growth factor. Conclusions. Through these paracrine effects, intravenously administered hUCMSCs reduced hepatic necrosis/apoptosis and enhanced liver regeneration. Thus, our data demonstrate that intravenously administered hUCMSCs may be useful in the prevention or treatment of acetaminophen-induced ALP.
引用
收藏
页码:1207 / 1219
页数:13
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