Establishment of Two Liver Fibrosis Models to Examine Endothelial Progenitor Cell Kinetics Establishment of Two Liver Fibrosis Models to Examine Endothelial Progenitor Cell Kinetics
Chronic inflammatory liver damage frequently induces irreversible liver fibrosis that eventually resultsin liver cirrhosis. Thus far, liver transplantation has been used as a non-optional treatment for patients with severeliver 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), haverecently been used to treat patients with liver cirrhosis as a means of liver regeneration therapy, however, there havebeen very few reports on EPC kinetics during the development of liver fibrosis. To investigate the relationshipbetween EPC kinetics and liver fibrosis, we have tried two murine models of inflammatory liver fibrosis, one createdby 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 exhibitedthe typical characteristics of liver fibrosis, including bridging fibrosis and pseudolobule formation, and splenomegalywas also observed. In addition, the blood levels of liver transaminases, alkaline phosphatase, andhyaluronic acid increased in the CCl4- injected mice, but not in the control mice. Importantly, EPC colony-formingassays showed a significant decrease in CFU-EPC numbers in both liver fibrosis models, suggesting that functionalEPC 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.
Chronic inflammatory liver damage frequently induces irreversible liver fibrosis that eventually resultsin liver cirrhosis. Thus far, liver transplantation has been used as a non-optional treatment for patients with severeliver 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), haverecently been used to treat patients with liver cirrhosis as a means of liver regeneration therapy, however, there havebeen very few reports on EPC kinetics during the development of liver fibrosis. To investigate the relationshipbetween EPC kinetics and liver fibrosis, we have tried two murine models of inflammatory liver fibrosis, one createdby 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 exhibitedthe typical characteristics of liver fibrosis, including bridging fibrosis and pseudolobule formation, and splenomegalywas also observed. In addition, the blood levels of liver transaminases, alkaline phosphatase, andhyaluronic acid increased in the CCl4- injected mice, but not in the control mice. Importantly, EPC colony-formingassays showed a significant decrease in CFU-EPC numbers in both liver fibrosis models, suggesting that functionalEPC 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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