Abstract
Ischemia/reperfusion injury (IRI) remains a major problem in organ transplantation, which represents the main cause of graft dysfunction posttransplantation. Hepatic IRI is characterized by an excessive inflammatory response within the liver. Mesenchymal stem cells (MSCs) have been shown to be immunomodulatory cells and have the therapeutic action on IRI in several organs. However, the mechanism of regulatory effect of MSCs on IRI remains unclear. In the present study, we examined the impact of MSCs on hepatic inflammatory response such as neutrophil influx and liver damage in a rat model of 70% hepatic IRI. Treatment with MSCs protected rat against hepatic IRI, with significantly decreased serum levels of liver enzymes, attenuated hepatic neutrophil infiltration, reduced expression of apoptosis-associated proteins, and ameliorated liver pathological injury. MSCs also significantly enhanced the intracellular activation of p38 MAPK phosphorylation, which led to decreased expression of CXCR2 on the surface of neutrophils. In addition, MSCs significantly diminished neutrophil chemoattractant CXCL2 production by inhibiting NF-κB p65 phosphorylation in macrophages. These results demonstrate that MSCs significantly ameliorate hepatic IRI predominantly through its inhibitory effect on hepatic neutrophil migration and infiltration.
Highlights
Liver transplantation is one of the most efficient life-saving treatments for various end-stage hepatic diseases [1]
Hepatic Ischemia/reperfusion injury (IRI) occurs in diverse clinical situations, such as hepatic resection, liver transplantation, shock, and trauma
Previous studies have shown that liver damage is mainly caused during reperfusion period, and neutrophils are considered central factors in the events leading to injury after reperfusion [19]
Summary
Liver transplantation is one of the most efficient life-saving treatments for various end-stage hepatic diseases [1]. Hepatic IRI remains a major problem in this clinical setting. IRI affects liver viability that usually leads to delayed recovery or even loss of graft function in liver transplantation [2]. IRI directly correlates to graft rejection, which causes up to 10% of early transplant failures and leads to a higher incidence of chronic rejection [3]. Hepatic IRI plays a critical role in donor shortage due to the higher sensitivity to IRI of clinical marginal liver donors. During hepatic IRI, liver damages are caused largely during the reperfusion period, when an excessive innate immune response is triggered by blood reperfusion [4]. Neutrophils are considered central factors in the events leading to injury after reperfusion [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
