2004 Fiscal Year Final Research Report Summary
HUMAN UMBILICAL CORD BLOOD-DERIVED CELLS DIFFERENTIATE INTO HEPATOCYTE-LIKE CELLS IN THE LIVER INJURY MODEL
| Project/Area Number |
14657293
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| Research Category |
Grant-in-Aid for Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
LI X-K. National Research Institute for Child Health and Development, Dept.of Innovative Surgery., Lab Head, 移植・外科研究部, 室長 (60321890)
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| Co-Investigator(Kenkyū-buntansha) |
FUJINO M. Natl.Inst.of Infectious Disease, AIDS Res.Ctr, Researcher, エイズ研究センター第二研究グルー, 研究員 (50392329)
奥山 虎之 国立成育医療センター(研究所), 遺伝診療科, 医長 (40177192)
EBATA T. Juntendo Univ.Sch.of Med., Dept.of Immunology, Asst.Prof, 医学部免疫学講座, 助手 (30343487)
OKUYAMA T. National Research Institute for Child Health and Development, Dept.of Clinical Genetics, Head (40177192)
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| Project Period (FY) |
2002 – 2004
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| Keywords | human umbilical cord blood / Stem cell / Hepatocyte / Fas-ligand / Liver iniury / NOD / Scid mice / Cell transplantation |
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| Research Abstract |
Background/Aims : Human umbilical cord blood (HUCB) contains stem/progenitor cells, which can differentiate into a variety of cell types. In this study, we investigated whether HUCB cells differentiate into hepatocytes in vitro and in vivo. We also examined CD34 could be the selection marker of stem cells for hepatocyte.
Methods : HUCB cells were obtained from normal full-term deliveries, and CD34+/-cells were further separated. For in vitro study, HUCB cells were cultured for 4 weeks, and expressions of liver specific genes were examined. For in vivo study, Non-obese diabetic/severe combined immunodeficient mice were subjected to liver injury by the Fas-ligand carried adenoviral vector or only to be radiated. The mice were treated simultaneously with or without cell transplantation of HUCB mononuclear cells, CD34^+ or CD34^- cells. After 4 weeks, the human specific gene/protein expression was examined.
Results : In vitro study, human liver specific genes were positive after 7 days culture. Immunofluorescent study showed positive staining of alpha-fetoprotein, cytokeratin 19 and albumin in round-shaped cells. In vivo study, immunohistochemical analysis showed human albumin, hepatocyte-specific antigen positive cells in mouse liver of Fas-ligand/transplantation group. Fluorescence in situ hybridization analysis using human Y chromosome showed positive signals. No difference between transplanted cell types was detected. However, immunopositive cells were not detected in the irradiated/transplantation group. Reverse transcription-polymerase chain reaction result also showed human hepatocyte specific gene expressions only in the Fas-ligand/transplantation group.
Conclusion : HUCB cells differentiated into hepatocyte-like cells in mouse liver, and liver injury was essential during this process. Both CD34^+ and CD34^- cells differentiated into hepatocyte-like cells and there was no difference between them.
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[Journal Article] Gene Expression Profile in the Regenerating Rat Liver after Partial Hepatectomy.2003
Author(s)
Y.Fukuhara, A.Hirasawa, X-K.Li, M.Kawasaki, M.Fujino, N.Funeshima, S.Katsuma, S.Shiojima, M.Yamada, T.Okuyama, S.Suzuki, G.Tsujimoto.
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Journal Title
J Hepatol 38(6)
Pages: 784-92
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomy2003
Author(s)
F.Xue, T.Takahara, Y.Yata, Y.Kuwabara, E.Shinno, K.Nonome, M.Minemura, S.Takahara, X-K.Li, E.Yamato, A.Watanabe.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
