Abstract:
Objective To investigate the effect of different transplantation approaches of human umbilical cord menchymal stem cells (HU-MSCs) on repairing hepatic ischemia-reperfusion injury (HIRI) in rat models.
Methods Forty male SD rats were randomly divided into the A (control group), B (model group), C (portal vein transplantation of MSCs group) and D (tail vein transplantation of MSCs group) groups (n=10 for each group). In the B, C and D groups, HIRI rat models were established by Pringle maneuver. MSC transplantation was not delivered in the B group, and chloromethyl-benzamidodialkylcarbocyanine (CM-DiL) labeled-HU-MSCs (106) were transplanted via portal vein or tail vein in the C or D groups. Blood samples were collected for detection of the expression levels of alanine aminotransferase(ALT) and tumor necrosis factor (TNF)-α before and 1, 3 and 5 d after transplantation. At 5 d post-transplantation, all rats in each group were sacrificed. The liver tissues were prepared for hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining for evaluation of liver injury. The distribution of HU-MSCs in the rat liver in each group was observed under laser confocal microscope.
Results After HU-MSCs transplantation, the expression levels of ALT in the C and D groups were significantly down-regulated compared with that in the B group, and the level of ALT in the C group was significantly lower than that in the D group (all P < 0.05). The expression levels of inflammatory cytokine TNF-α in the C and D groups were significantly lower than that in the B group and the TNF-α level in the C group was considerably lower than that in the D group (all P < 0.05). HE staining of the liver tissue prompted that the liver injury was the most severe in the B group, and the liver injury in the C group was less severe compared with that in the D group. TUNEL staining of the liver tissue revealed that the apoptosis index (AI) in the C and D groups was significantly lower than that in the B group, and the AI in the C group was significantly lower compared with that in the D group (all P < 0.05). Under laser confocal microscope, CM-DiL-labeled HU-MSCs were noted in the C and D groups after transplantation, and the quantity of HU-MSCs in the C group was significantly higher than that in the D group (all P < 0.05).
Conclusion Transplantation of HU-MSCs can mitigate the severity of HIRI. And transplantation via portal vein transplantation yields higher clinical efficacy compared with the tail vein route.