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2002 Fiscal Year Annual Research Report

新たなヒト化マウスの開発と再生医学への応用

Research Project

Project/Area Number 12357002
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

秦 順一  国立成育医療センター研究所, 所長 (90051614)

Co-Investigator(Kenkyū-buntansha) 清河 信隆  国立成育医療センター研究所, 形態発生研究室, 室長
山田 健人  慶應義塾大学, 医学部, 専任講師 (60230463)
藤本 純一郎  国立成育医療センター研究所, 発生・分化研究部, 部長
桜田 一洋  協和発酵工業株式会社, 東京研究所, 研究員
梅澤 明弘  国立成育医療センター研究所, 生殖医療研究部, 部長 (70213486)
Keywords再生 / 骨粗しょう症 / 腫瘍血管 / 肝炎 / 心筋 / 骨髄間質 / 細胞移植
Research Abstract

ヒト細胞をヒトに移植することで、本来の臓器の機能を補充することができる。このように臓器の機能を回復するために、細胞を導入することを「細胞移植」と呼ぶ。細胞移植は従来の臓器移植と異なり、他人の臓器そのものを移植しようと言う考えではなく、自分の細胞を含めた範囲の中で細胞レベルで臓器の機能を補填することを目指す。ここでは、骨髄中に存在する間質細胞が、細胞移植を行う上で有用であることを示す。
独自に樹立した骨髄間質細胞は、興味深いことに骨細胞、軟骨細胞脂肪細胞そして心筋細胞としての表現形質を示す。多分化能を有する間葉系細胞の幹細胞が骨髄中に存在することが予想され、他の興味深い分化能に関して試験管内にて検討した。同時に多分化能のうち、特に骨細胞、心筋細胞への分化について注目し、細胞を心筋、骨格筋ならびに骨欠損部位に移植した。移植後、短期および長期では、生体内において細胞は意外な分化能を示した。さらに、ヒト骨髄間質細胞をNOD/SCIDマウスに移植することに成功し、新たなヒト骨粗しょう症、ヒト腫瘍血管形成、また間質細胞の転換技術を用いた細胞移植系を確立した。
脱メチル化剤である5-azacytidineによる間質細胞の分化は不可逆的であり、再現性が高いシステムであることを、繰り返された実験で明らかにした。5-azacytidine以外の、他の効率の良い分化誘導剤または細胞転換剤の探索過程で多くの低分子化合物を試みた。この低分子化合物は必須であり、他の蛋白性物質では置き換えることはできなかった。しかし、蛋白性物質によりその転換の頻度を増減させることは可能であり、蛋白性物質は補助的な役割があると予想された。

  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] yabe, H., Fukuma, M., Urano, F., Yoshida, K., Kato, S., Hata, J.et al.: "Lack of matrix metalloproteinase(MMP)-1and 3expression in Ewing saarcoma may be due to loss of accessibility of the MMP regulatory element to the specific-"BBRC. 293. 61-71 (2002)

  • [Publications] Ambros, IM., Hata, J., Joshi, VV., Roald, B., Dehner, LP., Tuchler, H.et al.: "Morphologic Features of Neuroblastoma (Schwannian Stroma-Poor Tumors) in Clinic ally Favorable and Unfavorable Groups"cancer. 94. 1574-1583 (2002)

  • [Publications] Fukuzawa, A., Sakamoto, J., Heathcott, RW., Hata, J.: "A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7"J Med Genet. 39. 48-52 (2002)

  • [Publications] Ikeda, H., lehara, T., Tsuchida, Y., Kaneko, M., Hata.J.et al.: "Experience with International Neuroblastoma Staging System and Pathology Classi fication"Brit J Cancer. 86. 1110-1116 (2002)

  • [Publications] Nishimori, H., Sasaki, Y., Yoshida, K., Irifune, H., Hata, J.et al.: "The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors"Oncogene. 21. 8302-8309 (2002)

  • [Publications] Shibata, R., Hashiguchi, A., Sakamoto J., Umezawa, A., Hata, J.: "Correlation between a specific Wilms tumor suppressor gene (WT1) mutation and the histological findings in Wilms tumor (WT1)"J Med Genet. 39. e83-e87 (2002)

  • [Publications] Inoshita, S., Takeda, K., Hatai, K., Sano, Y., Hata, J.: "Phosshorylation and Inactivation of Mcl-1 by c-Jun N-teminal Kinase (JNK) in Response to Oxidative Stress"JBC. 277. 43730-43734 (2002)

  • [Publications] Fukuma, M., Hata, J., Umezawa, A.: "Id2 is a target of the EWS/ets chimeric protein in Ewing sarcoma family"Oncogene. 22. 1-9 (2003)

  • [Publications] fukuma, M., Abe, H., Okita, H., Yamada, T., Hata, J.: "Monoclonal antibody,4C4-mAb, specifically recognizes keratan sulfate proteog lycan on human embryonal carcinoma cells"J Pathol. (in press). (2003)

  • [Publications] Fukuzawa, R., Eccles, MR., Ikeda, M., Hata, J.: "Embryonal hyperplasia of Bowmann's capsular epithelium in patients with WT1 mutations"Pediatr Nephrol. 18. 9-13 (2003)

  • [Publications] Shibata, R., Umezawa, A., Takehara, K., Aoki, D., Nozawa, S., Hata, J.: "Primary carcinosarcoma of the vagina"Pathol Int. 53. 40-44 (2003)

  • [Publications] Shibata, R., Takata, A., Hashiguchi, A., Umezawa, A., Yamada, T., Hata, J.: "Responsiveness of chemotherapy based on the histologocal type and Wilms' tumor suppressor gene mutation in bilateral Wilms' tumor"Pathol Int. 53. 214-220 (2003)

  • [Publications] Tsunoda, K., Ota, T., Aoki, M., Yamada, T., Nagai, T., Nakagawa, T.et al.: "Induction of pemphigus phenotype by a monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3"J Immunology. 170. 2170-2178 (2003)

  • [Publications] Yuasa, H., Takakura, N., Shimomura, T., Suenobu, S., Yamada, I.et al.: "Analysis of human TlE2 function on hematopoietic stem cells in umbilical cord blood"BBRC. 298. 731-737 (2002)

  • [Publications] Nishimura, N., Nakayama, T., Tonoike, H., Yamada, T.et al.: "Various amplification of direct PCR using Blood Samples"Clinical Laboratory. 48. 377-384 (2002)

  • [Publications] Kakimoto, I., Hattori, Y., Okamoto, S., Yamada, T.et al.: "Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome"Jpn J Cancer Res. 93. 1029-1036 (2002)

  • [Publications] Zhao, C., Hashiguchi, A., Kondoh, K., Du W., Hata, J., Yamada T.: "Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response"Experimental Cellular Research. 275. 200-214 (2002)

  • [Publications] Sato, N., Hattori, Y., Du W., Yamada, T., Kamata, T.et al.: "Elevated level of basic fibroblast growth factor in multiple myeloma correlates with increased disease activity"Jpn J Cancer Res. 93. 459-466 (2002)

  • [Publications] Yamaoka, T., Yoshida, K., Yamada, T., Yano, M., Matsui, T., Hata, J.et al.: "Transgenic expression of FGF8 and FGF10 induces transdifferntiation of panceratic islet cells into hepatocytes and exocrine cells"BBRC. 292. 138-143 (2002)

  • [Publications] Fukao, T., Yamada, T., Tanabe, M., Terauchi, Y., Hata, J.et al.: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3r1 deficient mice"Nature Immunology. 3. 295-304 (2002)

  • [Publications] Matsuoka, K., Kiyokawa, N., Taguchi, Fujimoto, J.et al.: "Rum1, an inhibitor of cyclin-dependant kenase in fission yeast is negatively by mitogen-activated protein kinase-mediated phosphorylation at Ser and Thr residues"Eur-J-Biochem. 269. 3511-3521 (2002)

  • [Publications] Saito, M., Kiyokawa, N., Taguchi, T., Suzuki, K., Fujimoto, J.et al.: "Granulocyte Colony-stimulating Factor Directly Affects Human Monocytes and Modulates Cytokine Secretion"Exp-Hematol. 30. 1115-1123 (2002)

  • [Publications] Katagiri-U Y., Ohmi, K., Tang, W., Takenouchi, H., Fujimoto, J.et al.: "Raft.1, a monoclonal antibody raised against the raft microdomain, recognizes G-protein b1 and 2, which assemble near nucleus after Shiga toxin binding to human renal cell line"Lab-Inv. 82. 1735-1745 (2002)

  • [Publications] Nakao, H., Kataoka, C., Kiyokawa, N., Fujimoto, J., Yamasaki, S., Iakeda, T.: "Monoclonal antibody to shiga toxin 1,which blocks receptor binding and neutralizes cytotoxicity"Microbiol-Immunol. 777-780 (2002)

  • [Publications] Taguchi, T., Kiyokawa, N., Mimori, K., Suzuki, T., Fujimoto, J.et al.: "Pre-BCR-mekiated signal inhibits CD24-induced apptosis in human pre-B cells"J-Immunol. 170. 252-260 (2003)

  • [Publications] Mori, T., Kiyokawa, N., Shimada, H., Miyauchi, J., Fujimoto, J.: "Retrospective analysis of 34 patients diagnosed at the National Research Institute for Child Health and Development"Br-J-Haematol. (in press).

  • [Publications] Ohtomo, Y., Kawamura, R., Kaneko, K., Yamashiro, Y., Fujimoto, J.et al.: "Nephrotic syndrome associated with human parvovirus B19 infection"Pediatr Nephrol A. (in press).

  • [Publications] Mimori, K., Kiyokawa, N., Taguchi, T., Suzuki, T., Fujimoto, J.et al.: "Co-stimulatory signals distinctively affect CD20-and B-cell-antigen-receptor mediated apoptosis in Burkitt fs lymphoma/leukemia cells"Leukemia. (in press).

  • [Publications] Hakuno, D., Fukuda, D., Makino, S., Konishi, F., Umezawa, A.et al.: "Bone marrow-derived regenerated cardiomyocytes (CMG cells) express functional adrenergic and muscarnic receptors"Circulation. 105. 380-386 (2002)

  • [Publications] Ochi, K., Chen, G., Ushida, T., Gojo, S., Hata, J., Umezawa, A.et al.: "The use of osolate mature osteoblasts in abundance acts as desired-shaped bone regeneration in combination with a modified poly DL-lactic-co-glycokic acid (PLGA)-collagen sponge"J Cell Physiol. 194. 45-53 (2003)

  • [Publications] Suzuki, S., Tanaka, K., Nogawa, S., Umezawa, A., Hata, J.et al.: "Expression of interleukin-6 in cerebral neurons and ovarian cancer tissue in Trousseau syndrome"Clin Neuropathol. 21(5). 232-235 (2002)

  • [Publications] Inoshita, S., Takeda, K., Hatai, T., Hata, J., Umezawa, A.et al.: "Phosphorylation and Inactivation of Myeloid Cell Leukemia 1 by JNK in Response to Oxidative Stress"J Biological Chemistry. 277(46). 43730-43734 (2002)

  • [Publications] Imabayashi, H., Mori, T., Gojo, S., Hata, J., Umezawa, A.et al.: "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis"Exp Cell Res. (in press).

  • [Publications] Matsushita, K., Okita, H., Suzuki, A., Hata, J., Umezawa, A.et al.: "Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene"Mol Cell Endocr. (in press).

  • [Publications] Itoh, D., Yoneda, S., Kuroda, S., Kondo, H., Umezawa, A., Ohya, K.et al.: "Enhancement of osteogenes is on hydroxyapatite surface coated with synthetic peptide (EEEEEEEPRGDT) in vitro"J Biomed Mater Res. 62(2). 292-298 (2002)

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Published: 2004-04-07   Modified: 2016-04-21  

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