MESENCHYMAL STROMAL CELL THERAPY DURING EX VIVO LUNG PERFUSION AMELIORATES ISCHEMIA-REPERFUSION INJURY IN LUNG TRANSPLANTATION

ABSTRACT BACKGROUND The application of mesenchymal stromal cell (MSC)-based therapy during ex vivo lung perfusion (EVLP) could repair injured donor lungs prior to transplantation. The aim of this study was to determine the efficacy of MSC therapy performed during EVLP on ischemia-reperfusion injury using a pig lung transplant model. METHODS Following 24h of cold storage, pig lungs were randomly assigned to two groups (n=6 each): Control group - without MSC vs. MSC group - where 5 × 106 /kg MSCs were delivered through the pulmonary artery during EVLP. After 12h of EVLP, followed by a 1h second cold preservation period, the left lung was transplanted and reperfused for 4h. RESULTS EVLP perfusate hepatocyte growth factor (HGF) level at 12h was significantly elevated in the MSC group compared to the control, and was associated with a significant decrease in cell death markers - cleaved caspase-3 and TUNEL positive cells in the MSC group. The MSC group showed significantly lower IL-18 and IFN-γ levels and significantly higher IL-4 level in lung tissue at 12h of EVLP than the control group. After transplantation, the MSC group showed significant increase in lung tissue HGF level than the control group, associated with a significantly reduced lung tissue wet to dry weight ratio. Lung tissue TNF-α level and pathological acute lung injury score were significantly lower in the MSC group, compared to the control group. CONCLUSIONS The administration of MSCs ameliorated ischemic injury in donor lungs during EVLP and attenuated the subsequent ischemia-reperfusion injury after transplantation.