Effect of Stem Cells on Chromosomal Abnormalities Induced by CCl4 in Experimental Rat Liver Fibrosis

Abstract

Liver fibrosis, which is the main cause of many chronic liver diseases, is primarily characterized by an extensive deposition of ECM proteins (mainly type 1 collagen) in response to hepatic damage. The accumulation of collagen interferes with hepatic architecture and function which may subsequently progress into cirrhosis and liver failure. One commonly used hepatotoxin in the experimental studies of liver diseases is carbon tetrachloride (CCl4). It is a carcinogenic agent and induced genotoxicity in which its metabolites cause DNA strand break, chromosome aberrations (CAs) and sister chromatid exchanges. Advanced fibrosis is generally considered to be irreversible condition even after removal of the injurious agent. Moreover, the development of fibrosis is characterized by a diminution of liver collagenases activity, implying that the capacity of the diseased liver to remodel the fibrotic matrix is critically reduced. Currently, the only effective clinical therapy for end-stage liver diseases is orthotropic liver transplantation. However, several defects, such as surgical complexity, immunological rejection, low survival rate and particularly the shortage of donors' liver, preclude it from active use in clinics.