Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2005; 11(22): 3431-3440
Published online Jun 14, 2005. doi: 10.3748/wjg.v11.i22.3431
Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats
Dong-Chang Zhao, Jun-Xia Lei, Rui Chen, Wei-Hua Yu, Xiu-Ming Zhang, Shu-Nong Li, Peng Xiang
Dong-Chang Zhao, Rui Chen, Wei-Hua Yu, Xiu-Ming Zhang, Shu-Nong Li, Peng Xiang, Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, 74# Zhongshan Road II, Guangzhou 510080, Guangdong Province, China
Dong-Chang Zhao, Jun-Xia Lei, Wei-Hua Yu, Xiu-Ming Zhang, Shu-Nong Li, Department of Pathophysiology, Medical School of Sun Yat-Sen University, 74# Zhongshan Road II, Guangzhou 510080, Guangdong Province, China
Dong-Chang Zhao, Department of Pediatrics, Guangdong Province Maternal and Children’s Hospital, 13# Guangyuan Xilu, Guangzhou 510010, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Major State Basic Research Development Program of China (973 Program), No. 2001CB509904, the Key Scientific and Technological Projects of Guangdong Province, No. 2003A3020103, the Key Scientific and Technological Projects of Guangzhou City, No. 2002U13E0011, and the National Natural Science Foundation of China, No. 30100188
Correspondence to: Dr. Peng Xiang, Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, 74# Zhongshan Road II, Guangzhou 510080, Guangdong Province, China. pxiang@gzsums.edu.cn
Telephone: +86-20-87335822 Fax: +86-20-87335858
Received: December 20, 2004
Revised: December 21, 2004
Accepted: January 5, 2005
Published online: June 14, 2005
Abstract

AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats.

METHODS: MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN). There were two random groups on the 42nd d of CCl4:CCl4/MSCs, to infuse a dose of MSCs alone; CCl4/saline, to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCs on d 20. The morphological and behavioral changes of rats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR.

RESULTS: Compared to controls, infusion of MSCs reduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (20-40% vs 90%).The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR.

CONCLUSION: MSCs treatment can protect against experimental liver fibrosis in CCl4-induced or DMN-induced rats and the mechanisms of the anti-fibrosis by MSCs will be studied further.

Keywords: Mesenchymal stem cells; Liver fibrosis; Rat; Therapy