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, H2O2 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 H2O2. 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. (C) 2012 Elsevier Inc. All rights reserved.