Inoculation of murine bone marrow mesenchymal stem cells induces tumor necrosis in mouse with orthotopic hepatocellular carcinoma

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.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 x 10(5) 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.In MSCs group, the mean survival time was 25 days (95% Confidence interval: 22-28 d), while, in the control group, mean survival time was 21 days (95% CI: 20-23 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.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.PubMed05453-84