Infusion of human umbilical cord-derived mesenchymal stem cells effectively relieves liver cirrhosis in DEN-induced rats

Abstract

Cirrhosis is the long-term outcome of chronic hepatic injury and no effective therapy is currently available for this disease. Mesenchymal stromal cells (MSCs) are multi-potent cells that are easily acquired and amplified, and may be potential candidates for cell therapy against cirrhosis. This study aimed to determine the therapeutic effects of human umbilical cord-derived MSCs (hUCMSCs) for the treat ment of liver cirrhosis and identify an effective method for engrafting MSCs. The model of liver cirrhosis was established by induction of diethylnitrosamine (DEN) in rats. The isolated hUCMSCs were identified by morphology, flow cytometry and multilineage differentiation; they were injected into the vein of DEN-induced rats at varied cell doses and infusion times. Biochemical analyses of the serum and histopathological analysis of the liver tissues were performed to evaluate the therapeutic effects of hUCMSCs in all treatment groups. The results indicated that isolated hUCMSCs were capable of self-replication and differentiated into multiple lineages, including osteoblast-, adipocyte- and hepatocyte-like cells. Compared with the control group, administration of hUCMSCs at different cell doses and infusion times relieved DEN-induced cirrhosis to varying degrees. The therapeutic effects of hUCMSCs on liver cirrhosis gradually improved with increased cell dose and infusion times. The improvement of cirrhosis was due to the capacity of hUCMSCs to breakdown collagen fibers in the liver. It was demonstrated that infusion of hUCMSCs effectively relieved liver cirrhosis by facilitating the breakdown of collagen fibers in a dose-dependent manner and multiple infusions caused a relatively greater improvement in cirrhosis compared with a single infusion of hUCMSCs.