Allogeneic bone marrow-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury by suppressing oxidative stress and inhibiting apoptosis in rats

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to attenuate ischemia reperfusion (IR) injury in the heart, brain and kidney. However, their exact roles in the liver remain to be defined. Our objective was to investigate the potential effects of BM-MSCs on a hepatic IR rat model during the first 24h after reperfusion, a crucial period for hepatic IR damage formation. A rat model of normothermic partial hepatic ischemia was obtained by vascular clamping for 60min. BM-MSCs were transplanted via portal vein injection. Injury severity, oxidative stress response and apoptosis of liver cells were assessed at 2, 6, 12 and 24h after reperfusion and cell transplantation was evaluated. At 12 and 24h after reperfusion, rats transplanted with BM-MSCs had significantly lower serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), fewer damaged liver tissues, higher superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and lower malondialdehyde (MDA) levels compared to rats in the sham transplantation group. At 24h after reperfusion, IR rats transplanted with BM-MSCs had significantly fewer apoptotic hepatocytes, higher levels of B-cell lymphoma2 (Bcl-2) protein, and lower levels of Bcl-2-associatedX (Bax) and caspase-3 (Casp3) proteins compared to sham transplantation rats. In conclusion, BM-MSCs transplanted via the portal vein partially prevent hepatic IR injury by suppressing oxidative stress and inhibiting apoptosis during the first 24h after reperfusion.