Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats.
OBJECTIVE
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.


CONCLUSIONS
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.
Zhao
Dong-Chang
DC
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, 74# Zhongshan Road II, Guangzhou 510080, Guangdong Province, China.
Lei
Jun-Xia
JX
Chen
Rui
R
Yu
Wei-Hua
WH
Zhang
Xiu-Ming
XM
Li
Shu-Nong
SN
Xiang
Peng
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D004128:Dimethylnitrosamine; D018380:Hematopoietic Stem Cell Transplantation; D022781:Hepatocytes / Q000166:cytology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344
D002251:Carbon Tetrachloride; D004128:Dimethylnitrosamine