Basic studies on animal model for regenerative medicine using severe immunodeficient mice.
| Project/Area Number |
15300147
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Central Institute for Experimental Animals |
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Principal Investigator |
ITO Mamoru Central Institute for Experimental Animals, Laboratory of Immunology, Chief Researcher (00176364)
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| Co-Investigator(Kenkyū-buntansha) |
SOTOMARU Yusuke Central Institute for Experimental Animals, Laboratory of Animal Breeding Technologies, Researcher (90309352)
YAMADA Shuichi Kyoto University, Institute for Virus Research, Assistant (20261133)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2004: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2003: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Regenerative medicine / Animal model / NOG mice / ES cells / Rat / Differentiation / 再生医学 / 異種移植 / 同種移植 / 分化 |
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| Research Abstract |
We recently developed severe immunodeficient NOD/Shi-scid, IL-2Rγ KO (NOG) mice by introducing IL-2Rγ^<null> gene into NOD-scid mice. These mice show excellent development and differentiation of human cells, indicating the usefulness of NOG mice to generate "humanized mice". In this study, we investigated the use of NOG mice as models for regenerative medicine. For organ transplantation, human Graff follicles were developed when a small piece of human ovary was transplanted into a renal capsule. The menstrual cycle in the endometrium was also observed when human endometrial tissue was subcutaneously transplanted in the back of the mice followed by injection of human hormones. As a model for regenerative medicine using embryonic stem (ES) cells, we investigated in vivo differentiation of C57BL/6J-derived ES cells after their transplantation in various organs of NOG mice. When ES cells were injected into NOG lungs impaired by treatment with bleomycin or NOG livers impaired by treatment with carbon tetrachloride, ES cells grew and formed teratomas in the organs. However, differentiation of ES cells into lung or liver cells could not be confirmed. We also performed the same experiment using embryonic germ (EG) cells established from SD rats. After rat EG cells were injected into the lung of GFP transgenic SD rats impaired by treatment with bleomycin, the lung was removed and subcutaneously transplanted into the back of NOG mice. At 2, 4 and 8 weeks after transplantation, the implanted lungs were removed and examined histologically. As a result, the implanted lungs were partially engrafted, but the EG cells formed tereratomas. These results suggest that ES cells must be differentiated into progenitor cells but not ES cells by themselves for use in regenerative medicine.
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Report
(3 results)
Research Products
(56 results)
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[Journal Article] Hodgkin's lymphoma cells are efficiently engrafted and tumor marker CD30 is expressed with constitutive nuclear factor-kappaB activity in unconditioned NOD/SCID/gammac(null)mice2005
Author(s)
Dewan, M.Z., M.Watanabe, S.Ahmed, K.Terashima, S.Horiuchi, T.Sata, M.Honda, M.Ito, T.Watanabe, R.Horie, N.Yamamoto
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Journal Title
Cancer Sci 96
Pages: 466-473
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reproduction of menstrual changes in transplanted human endometrial tissue in immunodeficient mice2005
Author(s)
Matsuura-Sawada, R., T.Murakami, Y.Ozawa, H.Nabeshima, J.Akahira, Y.Sato, Y.Koyanagi, M.Ito, Y.Terada, K.Okamura
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Journal Title
Hum Reprod 20
Pages: 1477-1484
Description
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[Journal Article] Prompt tumor formation and maintenance of constitutive NF-kappaB activity of multiple myeloma cells in NOD/SCID/gammacnull mice2004
Author(s)
Dewan, M.Z., M.Watanabe, K.Terashima, M.Aoki, T.Sata, M.Honda, M.Ito, S.Yamaoka, T.Watanabe, R.Horie, N.Yamamoto
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Description
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[Journal Article] Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo2004
Author(s)
Hozumi, K., N.Negishi, D.Suzuki, N.Abe, Y.Sotomaru, N.Tamaoki, C.Mailhos, D.Ish-Horowicz, S.Habu, M.J.Owen.
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Journal Title
Nat Immunol 5
Pages: 638-644
Description
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[Journal Article] Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body2004
Author(s)
Kambe, N., H.Hiramatsu, M.Shimonaka, H.Fujino, R.Nishikomori, T.Heike, M.Ito, K.Kobayashi, Y.Ueyama, N.Matsuyoshi, Y.Miyachi, T.Nakahata
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Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Establishment of a new model of human multiple myeloma using NOD/SCID/gammac(null)(NOG)mice2004
Author(s)
Miyakawa, Y., Y.Ohnishi, M.Tomisawa, M.Monnai, K.Kohmura, Y.Ueyama, M.Ito, Y.Ikeda, M.Kizaki, M.Nakamura
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Journal Title
Biochem Biophys Res Commun 313
Pages: 258-262
Description
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[Journal Article] Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null)mice : suppression by an inhibitor against NF-kappaB2003
Author(s)
Dewan, M.Z., K.Terashima, M.Taruishi, H.Hasegawa, M.Ito, Y.Tanaka, N.Mori, T.Sata, Y.Koyanagi, M.Maeda, Y.Kubuki, A.Okayama, M.Fujii, N.Yamamoto
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Journal Title
J Virol 77
Pages: 5286-5294
Description
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[Journal Article] Functional CD5+ B cells develop predominantly in the spleen of NOD/SCID/gammac(null)(NOG)mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD34+ cells2003
Author(s)
Matsumura, T., Y.Kametani, K.Ando, Y.Hirano, I.Katano, R.Ito, M.Shiina, H.Tsukamoto, Y.Saito, Y.Tokuda, S.Kato, M.Ito, K.Motoyoshi, S.Habu.
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Journal Title
Exp Hematol 31
Pages: 789-797
Description
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[Journal Article] Fate of neural stem cells grafted into injured inner ears of mice2003
Author(s)
Tateya, I., T.Nakagawa, F.Iguchi, T.S., Kim, T.Endo, S.Yamada, R.Kageyama, Y.Naito, J.Ito.
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Journal Title
Neuroreport 14
Pages: 1677-1681
Description
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