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肝细胞生长因子基因转染的间充质干细胞对二甲基亚硝胺诱导的大鼠肝纤维化的影响。

Effects of hepatocyte growth factor gene-transfected mesenchymal stem cells on dimethylnitrosamine-induced liver fibrosis in rats.

作者信息

Moon Soung Hoon, Lee Chang Min, Park See-Hyoung, Jin Nam Myeong

机构信息

Department of Biological Science, Gachon University, Seongnam, Republic of Korea.

Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea.

出版信息

Growth Factors. 2019 Aug;37(3-4):105-119. doi: 10.1080/08977194.2019.1652399. Epub 2019 Aug 27.

DOI:10.1080/08977194.2019.1652399
PMID:31452434
Abstract

Nowadays, transplantation of human mesenchymal stem cells (MSCs) has emerged as a potential cellular therapy for liver cirrhosis. Hepatocyte growth factor (HGF) plays an important role in the regeneration of the liver. The objective of the study was to investigate the therapeutic effect of HGF-transfected human umbilical cord blood-derived MSCs on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. HGF-transfected MSCs were transplanted into rats with DMN-induced liver fibrosis. HO-induced cytotoxicity, apoptosis and intracellular reactive oxygen species were reduced in HGF-transfected MSCs in HGF-transfected MSCs. Pro-apoptotic proteins, such as cleaved poly (ADP-ribose) polymerase and cleaved caspase-3, were decreased in HGF-transfected MSCs. Biochemical analysis showed that the levels of aspartate aminotransferase and alanine aminotransferase were decreased after transplantation of HGF-transfected MSCs in rat fibrosis. Trichrome staining showed that HGF-transfected MSCs reduced liver damage. Taken together, our study indicated that HGF-transfected MSCs have therapeutic effects on DMN-induced liver fibrosis in rats.

摘要

如今,人骨髓间充质干细胞(MSCs)移植已成为一种潜在的肝硬化细胞治疗方法。肝细胞生长因子(HGF)在肝脏再生中起重要作用。本研究的目的是探讨HGF转染的人脐血来源的间充质干细胞对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化的治疗效果。将HGF转染的间充质干细胞移植到DMN诱导的肝纤维化大鼠体内。在HGF转染的间充质干细胞中,HGF诱导的细胞毒性、凋亡和细胞内活性氧减少。促凋亡蛋白,如裂解的聚(ADP-核糖)聚合酶和裂解的半胱天冬酶-3,在HGF转染的间充质干细胞中减少。生化分析表明,在大鼠肝纤维化模型中,移植HGF转染的间充质干细胞后,天冬氨酸转氨酶和丙氨酸转氨酶水平降低。三色染色显示,HGF转染的间充质干细胞减轻了肝脏损伤。综上所述,我们的研究表明,HGF转染的间充质干细胞对DMN诱导的大鼠肝纤维化具有治疗作用。

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