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Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with liver cirrhosis
Author(s) -
Maeda Masaki,
Takami Taro,
Terai Shuji,
Sakaida Isao
Publication year - 2012
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2011.07016.x
Subject(s) - medicine , cirrhosis , bone marrow , hepatocellular carcinoma , carbon tetrachloride , pathology , cancer research , gastroenterology , chemistry , organic chemistry
We have previously reported the efficacy and safety of autologous bone marrow cell infusion (ABM i ) therapy for liver cirrhosis patients without hepatocellular carcinoma in a multicenter clinical trial. However, since liver cirrhosis is highly oncogenic, evaluation of the effects of ABM i on the mechanisms of hepatocarcinogenesis is of great importance. Therefore, frequent ABM i was performed in hepatocarcinogenic mice, and its effects on hepatocarcinogenesis were analyzed. The N ‐nitrosodiethylamine (DEN)/green fluorescent protein (GFP)‐carbon tetrachloride (CCl 4 ) model was developed by administering DEN once, followed by repeated administration of CCl 4 intraperitoneally as for the control group. In the administration (ABM i ) group, GFP‐positive bone marrow cells were infused through a tail vein. The kinetics of hepatocarcinogenesis were evaluated histologically 4.5 months after DEN treatment. At 4.5 months, there was significantly lower incidence of foci and tumors in the ABM i group, and they were smaller in number, while their size was almost equal. No GFP‐positive tumors were found in ABM i livers. Moreover, ABM i livers showed significantly reduced liver fibrosis, consistent with significantly lower 8‐hydroxy‐2′‐deoxyguanosine levels, higher superoxide dismutase activity, and increased nuclear translocation of nuclear factor‐erythroid 2 p45‐related factor 2. These results demonstrate that frequent ABM i might contribute to suppressed tumor initiation during stages of hepatocarcinogenesis, consistent with improvements in liver fibrosis and stabilization of redox homeostasis.