Han fang Jiang1, Jun Ren. 1. Department of Medical Oncology, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing 100142, China.
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 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. RESULTS: 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. 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.
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 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. RESULTS: 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. 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.
Authors: Erika L Spaeth; Jennifer L Dembinski; A Kate Sasser; Keri Watson; Ann Klopp; Brett Hall; Michael Andreeff; Frank Marini Journal: PLoS One Date: 2009-04-07 Impact factor: 3.240