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Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis

间充质干细胞 医学 移植 生存素 标记法 细胞凋亡 肝移植 蛋白激酶B 男科 细胞生长 干细胞 病理 内科学 免疫组织化学 生物 癌症 生物化学 遗传学
作者
Jianfeng Sang,Xiaolei Shi,Bin Han,Tao Huang,Xu Huang,Haozhen Ren,Yitao Ding
出处
期刊:Hepatobiliary & Pancreatic Diseases International [Elsevier BV]
卷期号:15 (6): 602-611 被引量:36
标识
DOI:10.1016/s1499-3872(16)60141-8
摘要

Transplantation of mesenchymal stem cells (MSCs) has been regarded as a potential treatment for acute liver failure (ALF), but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection (InP group), hepatic intra-arterial injection (AH group), peripheral intravenous injection (PV group) and intrahepatic injection (IH group). The living conditions and survival time were recorded. Blood samples before and after MSCs transplantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) were analyzed by Western blotting. The average survival time of 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), respectively, when compared with the average survival time of 3.8±0.8 days in the D-Gal group. The survival rates between the InP group and D-Gal group revealed a statistically significant difference (P<0.01). Pathological and biochemical analysis showed that liver damage was the worst in the D-Gal group, while less injury in the InP group. Histopathological scores revealed a significant decrease in the InP group (3.17±1.04, P<0.01) and AH group (8.17±0.76, P<0.05) as compared with that in the D-Gal group (11.50±1.32). The apoptosis rate in the InP group (25.0%±3.4%, P<0.01) and AH group (40.5%±1.0%, P<0.05) was lower than that in the D-Gal group (70.6%±8.5%). The expression of active caspase-3 was inhibited, while the expression of survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) was elevated in the InP group. Intraportal injection was superior to other pathways for MSC transplantation. Intraportal MSC transplantation could improve liver function, inhibit apoptosis and prolong the survival time of swine with ALF. The transplanted MSCs may participate in liver regeneration via promoting cell proliferation and suppressing apoptosis during the initial stage of ALF.
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