Intra-portal transplantation of bone marrow stromal cells ameliorates liver fibrosis in mice

作     者：Zheng, Jin-Fang Liang, Li-Jian 

作者机构：Peoples Hosp Hainan Prov Dept Hepatobiliary Surg Haikou 570311 Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Dept Hepatobiliary Surg Guangzhou 510080 Peoples R China 

出 版 物：《Hepatobiliary & Pancreatic Diseases International》 (国际肝胆胰疾病杂志（英文版）)

年 卷 期：2008年第7卷第3期

页      面：264-270页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：bone marrow stromal cell hepatocyte differentiation cell therapy liver fibrosis 

摘      要：BACKGROUND: Bone marrow cells can differentiate into hepatocytes in a suitable microenvironment. This study was undertaken to investigate the effects of transplanted bone marrow stromal cells (BMSCs) on liver fibrosis in mice. METHODS: BMSCs were harvested and cultured from male BALB/c mice, then transplanted into female syngenic BALB/c mice via the portal vein. After partial hepatectomy, diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received BMSCs and non-supplemented drinking water, the model group received DEN with their water, and the experimental group received BMSCs and DEN. Mice were killed after 3 months, and ALT, AST, hyaluronic acid (HA), and laminin (LN) in serum and hydroxyproline (Hyp) in the liver were assessed. Alpha-smooth muscle actin (alpha-SMA) in the liver was assessed by immunohistochemistry. Bone marrow-derived hepatocytes were identified by fluorescent in situ hybridization (FISH) in liver sections. RESULTS: BMSCs were shown to differentiate into hepatocyte-like phenotypes after hepatocyte growth factor treatment in vitro. Serum ALT, AST, HA, and LN were markedly reduced by transplanted BMSCs. Liver Hyp content and alpha-SMA staining in mice receiving BMSCs were lower than in the model group, consistent with altered liver pathology. FISH analysis revealed the presence of donor-derived hepatocytes in the injured liver after cross-gender mouse BMSC transplantation. After three months, about 10% of cells in the injured liver were bone marrow-derived. CONCLUSION: BMSCs transplanted via the portal vein can convert into hepatocytes to repair liver injury induced by DEN, restore liver function, and reduce liver fibrosis.