Comparing different administration routes for mesenchymal stromal cell infusion in an in vivo porcine ischemia-reperfusion injury model
Hepatic ischemia-reperfusion injury is a complex pathophysiological process that occurs following reperfusion of blood supply in previously ischemic tissues. This form of injury plays a major role in cell dysfunction and death following hepatic surgery and liver transplantation. Mesenchymal stromal cells (MSC) seem to be a promising option for mitigation of this type of injury, as they possess anti-inflammatory and immune modulating capacities that may stimulate liver regeneration. The aim of this study was to demonstrate safety, feasibility and effectiveness of direct hepatic administration of MSC for treatment of ischemia-reperfusion injury in a pig model. After total vascular exclusion of the liver for 45 minutes, 3x10^6 human bone-marrow derived (BM)-MSC/kg were directly administrated into livers either via the intraportal route or hepatic artery route, whereas the control group did not receive any BM-MSC. Following reperfusion, hepatic blood flow and pulmonary pressures were continuously measured. Samples of blood and tissue of spleen, lung, and liver were taken among groups at the end of follow-up. Injection of BM-MSC did not result in obstruction of hepatic blood flow or increased pulmonary artery pressures. Blood flow in the portal vein was higher following injection BM-MSC in comparison to baseline blood flow. Arterially infused BM-MSC were more equal distributed over the different areas of the liver in comparison to the portal vein infused group (p=0,04). No BM-MSC were detected in pulmonary circulation nor in biopsies of spleen and lung. These results show that infusing therapeutic quantities of BM-MSC directly in the vascular bed of the liver is safe and feasible. Regarding risks of thrombosis or embolism, no differences between the routes of admission was observed. Overall design: to investigate the feasability, saety and effectiveness of Mesenchymal Stromal Cells (MSCs) as an anti-inflammatory and immune-modulating moiety for liver regeneration after ischemia, pig livers were infused with human MSCs to discriminate infused cells from recipient cells.. Liver damage and loss-of-function was monitored in blood samples, and biopsies were taken at baseline (no ischemia) and 6 hours after a period of 45' of ischemia for expression profiling and histology.