Infusion of Epithelial Progenitor Cells Ameliorates Hepatic Veno-Occlusive Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract

The purpose of this study is to evaluate the effect of epithelial progenitor cells (EPC) infusion on the development of hepatic veno-occlusive disease (HVOD) following allogeneic hematopoietic stem cell transplantation (HSCT). Mice received TBI (7.5 Gy with rate at 0.67 Gy/min) and then underwent HSCT without (n=20) or with the infusion of EPC (n=20) (HSCT+EPC). Untreated mice were used as control. Liver and whole blood were collected on d5 (day), d10, d15, d20 and d30 post HSCT and were used for the analysis of liver index, function (level of alanine transaminase (ALT) and total bilirubin (TBIL)) by Bio-Chemical Analyzer, pathology by H&E, immunohistochemical and Mason staining, liver ultrastructure by transmission electron microscope, platelet activation by flow cytometry as well as cytokine (TNF-a and IL-12) level by BDTM Cytometric Bead Array. Our results showed that on d30 post HSCT+EPC, liver index was not significantly different from control and was lower than HSCT alone (P < 0.05). Level of ALT and TBIL in HSCT+EPC were all significantly lower than HSCT with all higher than control on the 5 time points (P < 0.05), except ALT level on d30 with no difference compared to control (P > 0.05). Damage of liver sinusoids endothelial cell and central vein, necrosis of hepatocytes and fibrosis of liver sinusoids were observed in both groups with more severely in HSCT. The percentage of platelet activation (1.60±0.41%) and level of TNF-a (23.8±3.4 pg/ml) was significantly lower in HSCT+ EPC than HSCT alone (7.12±0.30% and 78.2±2.8 pg/ml, P < 0.05), but still higher than control (0.46±0.03% and 10.2±1.2 pg/ml, P < 0.05). Regarding the level of IL-12 in HSCT+EPC (19.7±0.1 pg/ml), it was significant lower than HSCT (71.9±5.3 pg/ml, P <0.05) with no difference compared to control (15.2±0.2 pg/ml, P > 0.05). In conclusion, infusion of EPC could ameliorate HVOD occurring after HSCT, possibly through endothelial cell repair, which led to improved liver function, reduced platelet activation and inflammatory cytokines release.