gms | German Medical Science

Introduction: A transplanted organ is up against immune response of the recipient but also stress and tissue damage caused by ischemia and reperfusion. Although a lot of effort has been made to identify the underlying pathomechanism of hepatic ischemia reperfusion injury (IRI), only little is known about the responsible cell populations. Here, we identified and characterized the infiltrating T-lymphocytes in a mouse model of hepatic ischemia reperfusion and determined the beneficial role of Mesenchymal Stem Cells (MSC) in this model.

Materials and methods: IRI of the liver was performed by clamping of the hepatic artery, the portal vein and the bile duct of various reporter and knock out mice for 45min (resulted in ischemia of about 70% of the liver). Blood, infiltrating cell and tissue analysis was done at 6, 24 and 72 hours after reperfusion. MSC therapy was performed by injecting 500,000 cells injected intravenously 2 hours before IRI.

Results: In this model we could identify and further characterize the role of T-lymphocytes in hepatic IRI. Therapy by exogenous MSC reduced this T-cell related early liver damage significantly as assessed by ALT measurement in blood serum samples. Expression of pro-inflammatory cytokines was also reduced after MSC administration and TNFα dependent expression of the adhesion molecule ICAM-1 was down regulated in MSC treated livers. Also, numbers of infiltrating T-cells were significantly lower after MSC therapy in IRI livers.

Conclusion: We could demonstrate a potential role of a specific T-lymphocyte subpopulation in the early hepatic ischemia reperfusion damage. MSC are potent inhibitors for IRI by modulating two sides of the lymphocyte dependent liver damage. On the one hand preventing lymphocytes from homing to the injured organ, on the other hand modulating the endothelium by down regulating adhesion molecules like ICAM-1. The presented data strengthen the beneficial use of MSC as novel cell therapeutics for solid organ transplantation.