Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats.
BACKGROUND
Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear.


METHODS
In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H(2)O(2) was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells.


RESULTS
The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H(2)O(2). In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection.


CONCLUSIONS
These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway.
Liver Transplantation Center, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Guo-zheng
GZ
Pan
Yang
Y
Yang
Jian
J
Zhang
Wei
W
Liu
Guo-ying
GY
Wang
Ying-cai
YC
Zhang
Qing
Q
Yang
Feng-xian
FX
Zhai
Yan
Y
Tai
Jian-rong
JR
Liu
Qi
Q
Zhang
Gui-hua
GH
Chen
D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy*
D006861:Hydrogen Peroxide