R Therapeutic effects and pathways of human umbilical cord mesenchymal stem cells transplantation for rat acute liver failure model

Abstract

Objective To explore the therapeutic effectiveness and pathways of human umbilical cord mesenchymal stem cells （hUCMSCs） transplantation for acute hepatic failure in rats. Method hUCMSCs were isolated from umbilical cord with attachment culture method, and the surface antigens were tested by flow cytometry. Forty-eight male Sprague Dawley rats were randomly divided into four groups. The animal model of acute liver failure was induced by injecting intraperitoneally with 50% olive oil solution of carbon tetrachloride （2. 5 ml/kg）. The treatment groups were injected with hUCMSCs suspension separately through the tail vein or injected into the liver 24 h post-modeling. Blood serum and liver tissues were collected at several time points to analyze the improvement of liver function and histological repair. Real-time PCR was used to detect the expression of human CK8, CK18 and AFP mRNA in liver tissues. Immunohistochemistry was used to detect the expression of human CK18 in liver tissues. Result There were statistically significant differences among liver functions after transplantation （P〈0. 05）. hUCMSCs improved histological status through enhancing hepatocellular regeneration and reducing inflammatory ceils. Real-time PCR results showed that the expression of CKS, CK18 and AFP mRNA was obviously increased in the tail vein transplantation group and hepatic lobe injection transplantation group as compared with the model group （P〈0. 05）. Immunochemistry results revealed that transplanted hUCMSCs in animal liver could differentiate into functional hepatocyte-like cells that expressed human CK18 as hepatocyte-specific marker in the tailvein transplantation group and hepatic lobe injection transplantation group. No significant differences in histological repair and grade of differentiation were examined between the tail vein transplantation group and hepatic lobe injection transplantation group （P〈0. 05）. Conclusion hUCMSCs can prompt the repair of acute liver failure and enhance pathological repair. Transplanted cells in animal liver can differentiate into functional hepatocyte-like cells that expressing hepatocyte-specific markers. Transplantation of hUCMSCs via the tail vein or direct injection into the liver had the similar therapeutic effects. Key words: Rat ; Liver failure; Mesenchymal stem cells; Transplantation