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Transplanted endothelial progenitor cells ameliorate carbon tetrachloride–induced liver cirrhosis in rats
Author(s) -
Liu Feng,
Liu ZhiDa,
Wu Nan,
Cong Xu,
Fei Ran,
Chen HongSong,
Wei Lai
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21845
Subject(s) - medicine , progenitor cell , cirrhosis , transplantation , carbon tetrachloride , albumin , liver regeneration , endothelial progenitor cell , liver transplantation , ex vivo , stem cell , in vivo , regeneration (biology) , biology , chemistry , microbiology and biotechnology , organic chemistry , genetics
Abstract Cirrhosis is the most common end stage of liver diseases, and there are no effective treatment methods. Here we evaluated the effect of endothelial progenitor cell (EPC) transplantation from rat bone marrow (BM) on the development of cirrhosis induced by carbon tetrachloride (CCl 4 ). Ex vivo generated, characterized, and cultivated rat BM–derived EPCs were identified by their vasculogenic properties in vitro. EPCs from male rats were transplanted into female rats via the intraportal vein 12 weeks after they had been challenged with CCl 4 , and the rats were killed 16 weeks later. The control rats received only a saline infusion. The fibrosis index and donor cell engraftment were assessed after EPC transplantation. After transplantation via the portal vein, PKH26 labeling, polymerase chain reaction, and in situ hybridization analysis revealed that the donor EPCs had adhered to the vasolateral surfaces of blood vessels and established in the liver. EPCs reduced the expression of α‐smooth muscle actin, collagen III, and transforming growth factor β ( P < 0.05) as well as levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the serum ( P < 0.05), but at the same time they increased the levels of albumin and Ki67. CCl 4 treatment increased the international prothrombin ratio ( P < 0.05) and reduced albumin levels, whereas EPCs restored these parameters to normal levels. These results suggest that EPC transplantation could play a role in regulating hepatocyte regeneration and ameliorating established liver cirrhosis. Liver Transpl 15:1092–1100, 2009. © 2009 AASLD.