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

ABSTRACT

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.