2001 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 Institution	National Research Institute for Child Health and Development
Principal Investigator	秦順一国立小児病院, (小児医療研究センター), センター長 (90051614)
Co-Investigator(Kenkyū-buntansha)	清河信隆国立小児病院, (小児医療研究センター)・病理研究室, 室長山田健人慶應義塾大学, 医学部, 専任講師 (60230463) 藤本純一郎国立小児病院, (小児医療研究センター)・病理病態研究部, 部長桜田一洋協和発酵工業株式会社, 東京研究所, 研究員梅澤明弘慶應義塾大学, 医学部, 助教授 (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ペルで臓器の機能を補填することを日指す。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
(37 results)

All Other

All Publications (37 results)

[Publications] Katagiri-U Y., Ohmi, K., Katagiri, C., Fujimoto, J., et al.: "Prominent inimunogenicity of monosialosyl galactosylgloboside, carrying a stage-specfic embryonic antigen-4(SSEA-4)-"Glycoconj-J. 18(4). 347-353 (2001)
[Publications] Nakajima, H., Kiyokawa, N., Fujimoto, J.et al.: "Kinetic analysis of binding between Shiga toxin and receptor gly colipid Gb3Cerby surface plasmon resonance"J. Biol-Chem. 276(46). 42915-42922 (2001)
[Publications] Ohmi, K., Kiyokawa, N., Sikino T., Fujimoto J.et al.: "Nitrobenzylthioinosine(NBT), a Nuoleoside Transport Inhibitor, Protects against ShigaToxin Cytotoxicity in Human Microvascular-"Endothelium (J. Endothol Cell Res). 8(4). 261-268 (2001)
[Publications] Nakajima, H., Katagiri-U Y., Fujimoto, J.et al.: "Single step method for puritication of Shiga toxin 1 B subumit using receptor mediated affinity chromatography by -"Protein Expression and Purification. 22(2). 267-275 (2001)
[Publications] Ebata, T., Mogi, S., Hata, Y., Fujimoto, J.et al.: "Rapid induction of CD95 ligand and CD4+T cell-mediated apoptosis by CD137(4-1BB) costimulation"Eur-J-lmmunol. 31. 1410-1416 (2001)
[Publications] Fujita, T., Yamada, T., Hashiguchi, A., Fujimoto, J.et al.: "Augmentation of megakaryocytopoiesis by the hematopoietic micro environment human granulocyte colony-stimulating factor -"Exp Hematol. 29. 1010-1018 (2001)
[Publications] Suzuki, T., Kiyokawa, N., Taguchi, T., Fujimoto, J.et al.: "CD24 induces apoptosis in human B cells via the GEM/rafts mediatd signaling system"J-Immunol. 166(9). 5567-5577 (2001)
[Publications] Katagiri-U Y., Kiyokawa, N., Fujimoto, J.: "The effect of Shiga Toxin binding to globotriaosyiceramide in rafts of human kidney cells and Burkitt's lymphoma Ramos cells"Trends-Glycosci-Glyc. 13. 281-290 (2001)
[Publications] Kiyokawa, N., Mori, T., Taguchi, T., Fujimoto, J.et al.: "Activation of the caspase cascade during Stxi-induced apoptosis in Burkitt's lymphoma cells"J-Cell-Biochem. 81(1). 128-142 (2001)
[Publications] Katagiri-U Y., Kiyokawa, N., Fujimoto, J.: "A role for lipid rafts in immune cell signaling. (review)"Microbiol-lmmunol. 45(1). 1-8 (2001)
[Publications] Sato, N., KiyoKawa, N., Takada, K., Fujimoto, J.et al.: "Characterization, of monoclonal antibodies against mouse and rat platelet glycoprotein V(CD42d)"Hybridoma. 19(6). 455-461 (2000)
[Publications] Fukuchi, T., Umezawa, A., Hata, J., et al.: "Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differntiation of CML cells"Oncogene. 20. 704-713 (2001)
[Publications] Ochi, K., Nozaki, H., Hata, J., Umezawa, A.et al.: "Specific bisulfite modification of CTG triiplet repeats of the androgen receptor gene, a gene associated with the triplet-"Neuroscience Research Communications. 28(1). 1-10 (2001)
[Publications] Hamatani, T., Sasaki, H., Hata, J., Umezawa, A.et al.: "Epigenetic mark sequence of the H19 gene in human sperm"Biochim Biophys Acta. 1518(1-2). 137-144 (2001)
[Publications] Sano, M., Umezawa, A., Abe, H., Hata, J.et al.: "EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing differentiation and apoptosis"Exp Cell Res. 266(1). 114-125 (2001)
[Publications] Shinoda, K., Yamada, T., Umezawa, A., Hata, J.et al.: "Light-induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apototic bcl-2-related-"Br J Ophthalmol. 85. 1237-1243 (2001)
[Publications] Fukuzawa, R., Umezawa, A., Morikawa, Y., Hata, J.et al.: "Nesidioblastosis and mixed hanartoma of the liver in Beckwith-Wiedemann syndrome : a case study including analysis of H19-"Peduatr Dev Pathol. 4(4). 381-390 (2001)
[Publications] Muto, A., Kizaki, M., Umezawa, A., Hata.J.et al.: "A novel differntiation-indUcing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF"Leukemia. 15(8). 1176-1184 (2001)
[Publications] Kohyama, J., Abe, H., Hata, J., Umezawa, A.et al.: "Brain from Bone : Efficient "meta-differntiation" of marrow stroma derived mature osteoblasts to neurons with noggin or a -"differentiation(Special issue on stem cells). 68. 235-244 (2001)
[Publications] Hakuno, D., Fukuda, D., Makino, S., Umezawa, A.et al.: "Bone marrow-derived regenerated cardiomyocytes(CMG cells) express functional adrenergic and muscarinic receptors"Circulation. 105. 380-386 (2002)
[Publications] Ohyama, M., Amagal, M., Hata, J., Umezawa, A.et al.: "Immunologic and histoopathologic characterization of active disease model mouse for pemphigus vulgaris"J Invest Dermatol. (in press).
[Publications] Sakamoto, J., Takata, A., Fukuzawa, R., Hata, J.et al.: "A Novel WTT Gene Mutation Associate with wilms Tumor and Congenital Male Genitourinary Malformation"PEDIATRIC RESARCH. 50(3). 337-344 (2001)
[Publications] Kitamura, k., Nagao, M., Yamada, T., Hata, J.et al.: "Dioxins in bile in relation to those in the human liver and blood"J Toxicological Sciences. 26(5). 327-336 (2001)
[Publications] Minh, T.B., Watanabe, M., Tanabe, S., Yamada, T., Hata, J.et al.: "specific accumulation and elimination kinetics of tris(4-chloropheny 1)methane, tris(4-chlorophny 1)methanol and other persistent -"Environmental Health Perspectives. 109(9). 927-935 (2001)
[Publications] Yamada, T., Hashiguchi, A., Umezawa, U., Hata, J.et al.: "Function of 90 kDa heat shock protein in cellitaar differentiation of human embryonal carcinoma cells"In Vitro Cell Dev Biol-Animal. 36. 139-146 (2000)
[Publications] Fujita, T., Yamada, T., Hasshiguchi, A., Hata, J., et al.: "Augmentation of megakaryocytopoiesis by the hematopoieticmicroen vironment of human granulocyte colony-stimulating factor -"Exp Hematol. 29. 1010-1018 (2001)
[Publications] Nishikai, K., Shimada, A., Iwanaga, S., Yamada, T.et al.: "Progression of cardiac dysfunction in a case of mitochondrial diabetes"Diabetes Care. 24(5). 960-961 (2001)
[Publications] Yamaoka, T., Yoshino, K., Yamada, T., Hata, J.et al.: "Diabetes and tumor formation in trasgenic mice expressing reg l"Biochem Biophys Res Commun. 278(2). 368-376 (2000)
[Publications] Zhao, C., Yamada, T., Kuramochi, S., Hata, J.et al.: "Two cases of ectopic hamartomatous thymoma"Virchows Archiv. 437. 643-647 (2000)
[Publications] Minh, T.B., Watanabe, M., Yamada, T., Hata, J.et al.: "Occurence of tris (4-chlorophenyl)methane, tris(4-chlorophnyl)methanol and some other persistent organochlorines in -"Environmental Health Perspectives. 108(7). 599-603 (2000)
[Publications] Yamaoka, T., Yano, M., Yamada, T., Matsushita, T.et al.: "Diabetes and pancreatic tumours in transgenic mice sxpressing Pax 6"Diabetologia. 43. 332-339 (2000)
[Publications] Fukushima, S., Yamada, T., Hashiguchi, A., Hata, J.et al.: "Augmentation of human leukemic cell invasion by the activation of small GTP-binding protein Rho"Exp Hematol. 28. 391-400 (2000)
[Publications] Shibata, M., Yamada, T., Tanahashi, N., Koto.A.et al.: "POEMS syndrome with necrotizing vasculitis : a novel feature of vascular abnomalities"Neurology. 54. 772-773 (2000)
[Publications] 山田健人: "血管新生の定量化"臨床検査. 44(13). 1534-1537 (2000)
[Publications] 山田健人: "ヒト腫瘍血管モデルとヒトがんの浸潤・移転モデル"病理と臨床. 19(7). 753-759 (2001)
[Publications] 山田健人: "進化を緩衝する分子HSP90の多面性"慶應医学. 77(1). 39-40 (2000)
[Publications] 山田健人, 秦順一: "ヒト腫瘍血管モデルとその分子機構"Surgery Frontier. 8(2). 36-41 (2001)

2001 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

Principal Investigator

秦 順一 国立小児病院, (小児医療研究センター), センター長 (90051614)

Research Products

[Publications] Katagiri-U Y., Ohmi, K., Katagiri, C., Fujimoto, J., et al.: "Prominent inimunogenicity of monosialosyl galactosylgloboside, carrying a stage-specfic embryonic antigen-4(SSEA-4)-"Glycoconj-J. 18(4). 347-353 (2001)

[Publications] Nakajima, H., Kiyokawa, N., Fujimoto, J.et al.: "Kinetic analysis of binding between Shiga toxin and receptor gly colipid Gb3Cerby surface plasmon resonance"J. Biol-Chem. 276(46). 42915-42922 (2001)

[Publications] Ohmi, K., Kiyokawa, N., Sikino T., Fujimoto J.et al.: "Nitrobenzylthioinosine(NBT), a Nuoleoside Transport Inhibitor, Protects against ShigaToxin Cytotoxicity in Human Microvascular-"Endothelium (J. Endothol Cell Res). 8(4). 261-268 (2001)

[Publications] Nakajima, H., Katagiri-U Y., Fujimoto, J.et al.: "Single step method for puritication of Shiga toxin 1 B subumit using receptor mediated affinity chromatography by -"Protein Expression and Purification. 22(2). 267-275 (2001)

[Publications] Ebata, T., Mogi, S., Hata, Y., Fujimoto, J.et al.: "Rapid induction of CD95 ligand and CD4+T cell-mediated apoptosis by CD137(4-1BB) costimulation"Eur-J-lmmunol. 31. 1410-1416 (2001)

[Publications] Fujita, T., Yamada, T., Hashiguchi, A., Fujimoto, J.et al.: "Augmentation of megakaryocytopoiesis by the hematopoietic micro environment human granulocyte colony-stimulating factor -"Exp Hematol. 29. 1010-1018 (2001)

[Publications] Suzuki, T., Kiyokawa, N., Taguchi, T., Fujimoto, J.et al.: "CD24 induces apoptosis in human B cells via the GEM/rafts mediatd signaling system"J-Immunol. 166(9). 5567-5577 (2001)

[Publications] Katagiri-U Y., Kiyokawa, N., Fujimoto, J.: "The effect of Shiga Toxin binding to globotriaosyiceramide in rafts of human kidney cells and Burkitt's lymphoma Ramos cells"Trends-Glycosci-Glyc. 13. 281-290 (2001)

[Publications] Kiyokawa, N., Mori, T., Taguchi, T., Fujimoto, J.et al.: "Activation of the caspase cascade during Stxi-induced apoptosis in Burkitt's lymphoma cells"J-Cell-Biochem. 81(1). 128-142 (2001)

[Publications] Katagiri-U Y., Kiyokawa, N., Fujimoto, J.: "A role for lipid rafts in immune cell signaling. (review)"Microbiol-lmmunol. 45(1). 1-8 (2001)

[Publications] Sato, N., KiyoKawa, N., Takada, K., Fujimoto, J.et al.: "Characterization, of monoclonal antibodies against mouse and rat platelet glycoprotein V(CD42d)"Hybridoma. 19(6). 455-461 (2000)

[Publications] Fukuchi, T., Umezawa, A., Hata, J., et al.: "Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differntiation of CML cells"Oncogene. 20. 704-713 (2001)

[Publications] Ochi, K., Nozaki, H., Hata, J., Umezawa, A.et al.: "Specific bisulfite modification of CTG triiplet repeats of the androgen receptor gene, a gene associated with the triplet-"Neuroscience Research Communications. 28(1). 1-10 (2001)

[Publications] Hamatani, T., Sasaki, H., Hata, J., Umezawa, A.et al.: "Epigenetic mark sequence of the H19 gene in human sperm"Biochim Biophys Acta. 1518(1-2). 137-144 (2001)

[Publications] Sano, M., Umezawa, A., Abe, H., Hata, J.et al.: "EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing differentiation and apoptosis"Exp Cell Res. 266(1). 114-125 (2001)

[Publications] Shinoda, K., Yamada, T., Umezawa, A., Hata, J.et al.: "Light-induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apototic bcl-2-related-"Br J Ophthalmol. 85. 1237-1243 (2001)

[Publications] Fukuzawa, R., Umezawa, A., Morikawa, Y., Hata, J.et al.: "Nesidioblastosis and mixed hanartoma of the liver in Beckwith-Wiedemann syndrome : a case study including analysis of H19-"Peduatr Dev Pathol. 4(4). 381-390 (2001)

[Publications] Muto, A., Kizaki, M., Umezawa, A., Hata.J.et al.: "A novel differntiation-indUcing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF"Leukemia. 15(8). 1176-1184 (2001)

[Publications] Kohyama, J., Abe, H., Hata, J., Umezawa, A.et al.: "Brain from Bone : Efficient "meta-differntiation" of marrow stroma derived mature osteoblasts to neurons with noggin or a -"differentiation(Special issue on stem cells). 68. 235-244 (2001)

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

[Publications] Ohyama, M., Amagal, M., Hata, J., Umezawa, A.et al.: "Immunologic and histoopathologic characterization of active disease model mouse for pemphigus vulgaris"J Invest Dermatol. (in press).

[Publications] Sakamoto, J., Takata, A., Fukuzawa, R., Hata, J.et al.: "A Novel WTT Gene Mutation Associate with wilms Tumor and Congenital Male Genitourinary Malformation"PEDIATRIC RESARCH. 50(3). 337-344 (2001)

[Publications] Kitamura, k., Nagao, M., Yamada, T., Hata, J.et al.: "Dioxins in bile in relation to those in the human liver and blood"J Toxicological Sciences. 26(5). 327-336 (2001)

[Publications] Minh, T.B., Watanabe, M., Tanabe, S., Yamada, T., Hata, J.et al.: "specific accumulation and elimination kinetics of tris(4-chloropheny 1)methane, tris(4-chlorophny 1)methanol and other persistent -"Environmental Health Perspectives. 109(9). 927-935 (2001)

[Publications] Yamada, T., Hashiguchi, A., Umezawa, U., Hata, J.et al.: "Function of 90 kDa heat shock protein in cellitaar differentiation of human embryonal carcinoma cells"In Vitro Cell Dev Biol-Animal. 36. 139-146 (2000)

[Publications] Fujita, T., Yamada, T., Hasshiguchi, A., Hata, J., et al.: "Augmentation of megakaryocytopoiesis by the hematopoieticmicroen vironment of human granulocyte colony-stimulating factor -"Exp Hematol. 29. 1010-1018 (2001)

[Publications] Nishikai, K., Shimada, A., Iwanaga, S., Yamada, T.et al.: "Progression of cardiac dysfunction in a case of mitochondrial diabetes"Diabetes Care. 24(5). 960-961 (2001)

[Publications] Yamaoka, T., Yoshino, K., Yamada, T., Hata, J.et al.: "Diabetes and tumor formation in trasgenic mice expressing reg l"Biochem Biophys Res Commun. 278(2). 368-376 (2000)

[Publications] Zhao, C., Yamada, T., Kuramochi, S., Hata, J.et al.: "Two cases of ectopic hamartomatous thymoma"Virchows Archiv. 437. 643-647 (2000)

[Publications] Minh, T.B., Watanabe, M., Yamada, T., Hata, J.et al.: "Occurence of tris (4-chlorophenyl)methane, tris(4-chlorophnyl)methanol and some other persistent organochlorines in -"Environmental Health Perspectives. 108(7). 599-603 (2000)

[Publications] Yamaoka, T., Yano, M., Yamada, T., Matsushita, T.et al.: "Diabetes and pancreatic tumours in transgenic mice sxpressing Pax 6"Diabetologia. 43. 332-339 (2000)

[Publications] Fukushima, S., Yamada, T., Hashiguchi, A., Hata, J.et al.: "Augmentation of human leukemic cell invasion by the activation of small GTP-binding protein Rho"Exp Hematol. 28. 391-400 (2000)

[Publications] Shibata, M., Yamada, T., Tanahashi, N., Koto.A.et al.: "POEMS syndrome with necrotizing vasculitis : a novel feature of vascular abnomalities"Neurology. 54. 772-773 (2000)

[Publications] 山田健人: "血管新生の定量化"臨床検査. 44(13). 1534-1537 (2000)

[Publications] 山田健人: "ヒト腫瘍血管モデルとヒトがんの浸潤・移転モデル"病理と臨床. 19(7). 753-759 (2001)

[Publications] 山田健人: "進化を緩衝する分子HSP90の多面性"慶應医学. 77(1). 39-40 (2000)

[Publications] 山田健人, 秦 順一: "ヒト腫瘍血管モデルとその分子機構"Surgery Frontier. 8(2). 36-41 (2001)

秦順一国立小児病院, (小児医療研究センター), センター長 (90051614)

[Publications] 山田健人, 秦順一: "ヒト腫瘍血管モデルとその分子機構"Surgery Frontier. 8(2). 36-41 (2001)