Original Article : Establishment of Two Liver Fibrosis Models to Examine Endothelial Progenitor Cell Kinetics
의약학 > 의공학
( Katsuya Shirakura ) , ( Sang Mo Kwon ) , ( Haruchika Masuda ) , ( Syotaro Obi ) , ( Rie Ito ) , ( Tomoko Shizuno ) , ( Yusuke Kurihara ) , ( Tetsuya Mine ) , ( Takayuki Asahara )
조직공학과 재생의학 2009년, 제6권 제12호, 1128~1133페이지(총6페이지)
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    Chronic inflammatory liver damage frequently induces irreversible liver fibrosis that eventually results in liver cirrhosis. Thus far, liver transplantation has been used as a non-optional treatment for patients with severe liver cirrhosis, although there are several drawbacks, including the shortage of donors and invasiveness of the operation. Bone marrow or peripheral blood derived stem cells, including endothelial progenitor cells (EPCs), have recently been used to treat patients with liver cirrhosis as a means of liver regeneration therapy, however, there have been very few reports on EPC kinetics during the development of liver fibrosis. To investigate the relationship between EPC kinetics and liver fibrosis, we have tried two murine models of inflammatory liver fibrosis, one created by injecting carbon tetrachloride (CCl4) intraperitoneally and the other created by injecting CCl4 subcutaneously. Examination of hematoxylin-eosin and azan stained sections of the animals` liver confirmed that both models exhibited the typical characteristics of liver fibrosis, including bridging fibrosis and pseudolobule formation, and splenomegaly was also observed. In addition, the blood levels of liver transaminases, alkaline phosphatase, and hyaluronic acid increased in the CCl4- injected mice, but not in the control mice. Importantly, EPC colony-forming assays showed a significant decrease in CFU-EPC numbers in both liver fibrosis models, suggesting that functional EPC bioactivity in the bone marrow may be dramatically down-regulated in inflammatory liver fibrosis. In conclusion, our models provide information on EPC biology in chronic inflammatory liver disease that induces liver fibrosis.
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