Human umbilical cord-derived mesenchymal stem cell tansplantation for liver fibrosis and cirrhosis / 中国组织工程研究

ABSTRACT

BACKGROUND:Cirrhosis is a long-term consequence of chronic hepatic injury, which has no effective therapy. Mesenchymal stem cels have been shown to play a potential role in the treatment of liver fibrosis/cirrhosis. OBJECTIVE:To investigate the therapeutic effect and mechanism of human umbilical cord-derived mesenchymal stem cels on CCl4 induced liver fibrosis/cirrhosis in rats. METHODS:A CCl4-induced liver fibrotic/cirrhotic rat model was used, and human umbilical cord-derived mesenchymal stem cels were injectedvia the tail vein after modeling. Liver biochemical profile was measured by Beckman Coulter analyzer. Histopathological changes were assessed by Sirius red staining. The expressions of colagen type I, colagen type III, matrix metaloproteinases-2 and tissue inhibitor of matrix metaloproteinases-2 protein and mRNA in liver tissues were observed by immunohistochemistry, western blot and real-time PCR, respectively. RESULTS AND CONCLUSION:Liver biochemical profile indicated the transplantation of human umbilical cord-derived mesenchymal stem cels could improve the liver function of rats with liver fibrosis and cirrhosis. After cel transplantation, except 1-week cel transplantation group, the expressions of the matrix metaloproteinases-2 mRNA and protein were significantly increased, while the expressions of colagen type I, colagen type III and tissue inhibitor of matrix metaloproteinases-2 mRNA and protein significantly decreased, compared with the corresponding model groups. Human umbilical cord-derived mesenchymal stem cels play a role in the treatment of liver fibrosis and cirrhosis through upregulating the expression of matrix metaloproteinases-2 and lowering the expression of inhibitor of matrix metaloproteinases-2. With the continued presence of pathogenic factors, human umbilical cord-derived mesenchymal stem cel transplantation cannot reverse liver fibrosis or cirrhosis, and only delay the process of liver fibrosis or cirrhosis.