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人 CD34(+) 干细胞/祖细胞移植逆转大鼠肝纤维化。

Reversal of Hepatic Fibrosis by Human CD34(+) Stem/Progenitor Cell Transplantation in Rats.

机构信息

Departments of Medical Biochemistry, Faculty of Medicine, Ain Shams University.

Medical Biochemistry, Faculty of Medicine, Ain Shams University.

出版信息

Int J Stem Cells. 2010 May;3(2):161-74. doi: 10.15283/ijsc.2010.3.2.161.

Abstract

Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation. Here, we transplant UCB cells into injured liver fibrosis, investigated the hepatic potential of UCB cells both in vitro and in vivo. a CCl4 rat model with liver fibrosis was prepared. Human (UCB) CD34(+) stem cell was separated with MACS (magnetic cell sorting). Cells were cultured with and without hepatic differentiation medium. Rats were divided into 3 groups; group (1): control healthy, group (2): CCl4 injected rats and group 3: CCl4/CD34(+)injected rats with human differentiated and undifferentiated cells through intrahepatic (IH) and intravenous (IV) routes. A significant elevation was detected in serum albumin in CCl4/CD34(+) compared to the CCl4 group (p<0.001). Serum ALT, had a significant decrease of its level after administration of stem cells compared to the CCl4 group (p<0.001). However, it was still significantly higher than control (p<0.001) with no significant difference between the groups that received stem cells. Histopathological examination of liver tissue showed that stem cells have a significant antifibrotic effect. Concerning gene expression, the collagen gene (rat) was highly expressed in the CCl4 group whereas its expression was significantly decreased after administration of stem cells. Human albumin and matrix metalloproteinase (MMP2) genes were expressed in liver tissues in the groups that received stem cells. Highest expression was in the group that received un-differentiated cells I.V. human UCB CD34(+) stem cells can ameliorate liver fibrosis in rats.

摘要

人脐带血(UCB)细胞作为细胞移植移植物具有许多优势。在这里,我们将 UCB 细胞移植到损伤的肝纤维化中,研究了 UCB 细胞在体外和体内的肝潜能。制备了 CCl4 诱导的大鼠肝纤维化模型。用 MACS(磁细胞分选)分离人(UCB)CD34(+)干细胞。细胞在有和没有肝分化培养基的情况下进行培养。大鼠分为 3 组:组 1:健康对照组,组 2:CCl4 注射大鼠组和组 3:通过肝内(IH)和静脉(IV)途径注射 CCl4/CD34(+)的大鼠。与 CCl4 组相比,CCl4/CD34(+)组血清白蛋白明显升高(p<0.001)。与 CCl4 组相比,干细胞给药后血清 ALT 水平显著降低(p<0.001)。然而,与对照组相比,其水平仍然显著升高(p<0.001),而接受干细胞的各组之间没有显著差异。肝组织学检查显示,干细胞具有显著的抗纤维化作用。关于基因表达,胶原基因(大鼠)在 CCl4 组中高度表达,而在给予干细胞后其表达显著降低。在接受干细胞的各组中,肝脏组织中表达了人白蛋白和基质金属蛋白酶(MMP2)基因。未分化细胞静脉内给药的组表达最高。人 UCB CD34(+)干细胞可改善大鼠肝纤维化。

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