Bone marrow mononuclear cell transplant therapy in mice with CCl4-induced acute liver failure.

BACKGROUND/AIMS: Stem cell transplantation has theoretical potential for the treatment of certain liver diseases. However, the use of bone marrow mononuclear cells as a therapy for liver disease has received little attention. The present study was to examine whether bone marrow mononuclear cells might be useful in the management of acute liver failure in an animal model. MATERIALS AND METHOTS: Bone marrow mononuclear cells were harvested from BALB/c mice and then labeled with the fluorescent dye PKH26. The labeled cells were subsequently infused into the tail veins of mice in which hepatic injury had been induced by CCl4 toxicity. After transplantation, the labeled cells in the liver were studied by fluorescent microscopy, and the levels of proliferating cell nuclear antigen and albumin were quantified in bone marrow mononuclear cell-treated and untreated groups. Serum aminotransferase activity was also monitored at various time points post-liver injury. RESULTS: Transplanted bone marrow mononuclear cells labeled with PKH26 were found to populate the damaged liver around the portal and centrolobular regions, and they appeared to differentiate into albumin-producing hepatocyte-like cells. Animals that received bone marrow mononuclear cells also showed a trend toward improved liver enzymes as well enhanced survival rates, relative to controls. CONCLUSIONS: These findings suggest that systemically delivered bone marrow mononuclear cells may relocate to and be retained by the injured liver; transplantation of bone marrow mononuclear cells showed an overall beneficial effect in a murine model of acute liver failure.

Study on transplantation of induced bone marrow mesenchymal stem cells via various route for the treatment of chronic liver injury / 中华消化杂志

Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via various route for treatment of chronic liver injury.Methods MSCs were isolated and expanded by density gradient centrifugation combined with adherent culture.MSCs were induced to differentiate into hepatocyte-like cells in vitro.The markers of hepatocyte lineage were examined by RT-PCR and immunocytochemistry.The changes of ultramicrostructure of MSCs were observed by transmission electron microscope.One hundred and fourteen Wistar rats were treated with mixture of 40%CCl4 and peanut oil to establish chronic liver injury model and another 6 rats were served as control.Twelve rats in model group were died within 8 weeks,and the rest rats were divided into portal vein,spleen and tail vein transplantation groups.The rats were transplanted with DAPI-labelled MSCs which were induced for 14 days.The distribution of the DAPI-labelled cells were observed by fluorescence microscopy.The liver function and pathology were examined.Results AFP mRNA expression were detected at 7th and 14th day after induction,expressions of ALB mRNA,CK18 and hepatocyte antigen were found at 14th and 2lth day.The ultrastructure examination revealed that MSCs were enlarged with a lot of endoplasmic reticulum,mitochondrion,lysosome and glycogen granule.DAPI labelled cells were found in the spleen and liver transplantion groups.The pathological changes of liver were alleviated in all treated groups,especially in intraspleenic transplantion group(P＜0.05).Conclusions Induced bone marrow MSCs can ameliorate liver function of chronic hepatic injury after transplantation.The intraspleenic transplantation is better than others.