Inoculation of murine bone marrow mesenchymal stem cells induces tumor necrosis in mouse with orthotopic hepatocellular carcinoma / 北京大学学报(医学版)

ABSTRACT

Objective:To observe whether murine bone marrow mesenchymal stem cells(MSCs)implantation improves the survival of hepatocellular carcinoma(HCC)-bearing mice,and to investigate whether MSCs can differentiate to hepatocytes in HCC microenvironment in a mouse model of orthotopic HCC and its effects on tumor cells.Methods:Murine bone morrow MSCs were obtained through adherent culture method combined with magnetic cell sorting CD45-,CD11b-cells,labeled with CFSE in vitro.Phenotypes of MSCs were analyzed by flow cytometry.A murine model of orthotopic HCC was induced by intrahepatic injection of 5?105 murine H22 hepatoma cells in a BALB/c mouse.In this experiment,twelve BALB/c mice were randomly divided into MSCs implantation and saline administration groups on the 7th day after establishment of orthotropic HCC.CFSE labeled MSCs were injected into tumor and/or normal liver tissue in MSCs implantation group.The life span of HCC-bearing mice was observed.After three weeks,albumin was determined by immunohistochemistry.The livers of HCC-bearing mice were observed by light microscopy.Results:In MSCs group,the mean survival time was 25 days(95%Confidence interval22-28 d),while,in the control group,mean survival time was 21 days(95%CI20-23 d).However,the statistical difference was not obvious between the two groups(P=0.0713).It showed that the CFSE labeled cells mainly localized in the border of tumor,also a few in the tumor bed,and expressed albumin.Interestingly,there was a larger area of necrosis in the tumor bed,compared with that in the controls.Conclusion:It can be concluded that MSCs not only could engraft in livers of carcinoma-bearing BALB/c mice,but also could differentiate to hepatocyte-like cell.At the same time,MSCs might induce tumor cells necrosis.Further mechanism need to be studied.