Transplantation routes and mechanism of mesenchymal stem cell therapy in porcine models with acute liver failure / 中华肝胆外科杂志

ABSTRACT

Objective To explore the most effective route of mesenchymal stem cell transplantation (MSCs) in D-galactosamine (D-gal) induced porcine model with acute liver failure (ALF) and the potential mechanism.Methods BA-MA mini-pigs with D-gal-induced ALF were transplanted with porcine mesenchymal stem cells (MSCs) through four routesintraportal injection (InP),peripheral intravenous injection (PV),hepatic intra-arterial injection (AH) and intrahepatic injection (IH).The survival time was recorded.The blood samples before and after MSC transplantation were collected for detecting liver function.Liver histology was interpreted and scored.Hepatic apoptosis and regeneration were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and Ki-67 assay.The protein expression of cleaved caspase-3,survivin,AKT and ERK were analyzed by Western blot.Results The average survival time in each group was (10.7 ±1.6) days (InP),(6.0 ±0.9) days (AH),(4.7 ±1.4) days (PV),(4.3 ± 0.8) days (IH) when compared with D-gal group [(3.8 ± 0.8) days].The histopathological scores revealed a significantly decrease in InP group (3.17 ± 1.04,P ＜0.05) and AH group (8.17 ± 0.76,P ＜ 0.05) when compared with that in D-gal group (11.50 ± 1.32).The apoptosis rate in InP group (25.0 ± 3.4％,P ＜ 0.05) and AH group (40.5 ± 1.0％,P ＜ 0.05) was lower than that in D-gal group (70.6 ± 8.5％).The expression of active caspase-3 was inhibited,while the expression of survivin,AKT and ERK was elevated in InP group.Conclusions The intraportal injection was superior to other pathways for MSCs transplantation.Intraportal MSC transplantation could improve liver function,inhibit cell apoptosis,promote cell proliferation and prolong the survival in porcine ALF model.