2000 Fiscal Year Annual Research Report

サル胚性幹細胞からの器官特異的機能細胞の分化誘導法の開発

Research Project

Project/Area Number	12557067
Research Institution	The University of Tokyo
Principal Investigator	辻浩一郎東京大学, 医科学研究所, 助教授 (50179991)
Co-Investigator(Kenkyū-buntansha)	田中竜平国立がんセンター研究所, 生物学部細胞生物研究室, 室長(研究職) (80322072)
Keywords	サル胚性幹細胞 / 造血幹細胞 / AGM領域 / ストローマ
Research Abstract	サル胚性幹細胞から造血幹細胞への分化を誘導するための微細環境として、従来より用いられてきた線維芽細胞は不適当と考えられた。そこで我々は、胎生期マウスのAGM(aorta-gonad-mesonephros)領域に注目した。 (1)マウスAGM(aorta-gonad-mesonephros)領域由来ストローマ細胞株の樹立胎生期マウス造血においては、成体マウス造血を再構築し得る二次造血幹細胞は、胎生10〜11日のAGM領域にはじめて認められることより、この時期のAGM領域には、二次造血幹細胞の発生を支持する分子(群)が発現していると考えられる。そこで、胎生10.5日のAGM領域よりストローマ細胞株、AGM-S3細胞を樹立した。 (2)AGM-S3細胞の造血発生支持能の検討胎生8.5日のAGM領域に相当するPAS(paraaortic splanchnopleura)及び卵黄嚢から分離した細胞を、AGM-S3細胞上で共培養した後、Ly-5.1/5.2マウス移植系を用いて、成体マウスの二次造血を再構築し得る二次造血幹細胞の発生について検討した。その結果、いずれの細胞の共培養系においても、培養4日目頃より二次造血幹細胞が出現した。以上の結果より、AGM-S3細胞にはPASあるいは卵黄嚢からの造血幹細胞の発生を支持する分子(群)が発現されていると考えられた。また、AGM-S3細胞は、マウスばかりでなく、ヒトの造血幹細胞にも作用することが示されており、サル胚性幹細胞からの造血幹細胞の発生にも有用であると予想された。

Research Products
(37 results)

All Other

All Publications (37 results)

[Publications] Ueda T.: "Expansion of human NOD/SCID-repopulating cells by a combination of stem cell factor, Flk2/Flt3 ligand, thrombopoietin and a complex of interleukin-6 and soluble interleukin-6 receptor."J.Clin.Invest.. 105. 1013-1021 (2000)
[Publications] Hayashi Y.: "SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3."Cancer Res.. 60. 1139-1145 (2000)
[Publications] Ebihara Y.: "Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34^+ cells."Br.J.Haematol.. 109. 153-161 (2000)
[Publications] Ueda T.: "Hematopoietic repopulating ability of cord blood CD34^+ cells in NOD/Shi-scid mice."Stem Cells. 18. 204-213 (2000)
[Publications] Ueda T.: "Massive pericardial and pleural effusion with anasarca following allogeneic bone marrow transplantation."Int.J.Hematol.. 71. 394-397 (2000)
[Publications] Sato T.: "Erythroid progenitors differentiate and mature in response to endogenous erythropoietin."J.Clin.Invest.. 106. 263-270 (2000)
[Publications] Ishii T.: "Improvement in bronchiolitis obliterans organizing pneumonia by combination of oral predonisolone and low dose erythromycin in a child after allogegeneic bone marrow transplantation."Bone Marrow Transplant. 26. 907-910 (2000)
[Publications] Sugiyama H.: "Peroxisome proliferator-activated receptors are expressed in mouse bone marrow-derived mast cells."FEBS Lett.. 467. 259-262 (2000)
[Publications] Yoshino H.: "Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice."Bone Marrow Transplant.. 26. 1211-1216 (2000)
[Publications] Takaki S.: "Control of B cell production by the adaptor protein Lnk, a negative regulator of tyrosine kinase signaling."Immunity. 13. 599-609 (2000)
[Publications] Matsui A.: "gp130 and c-kit signals synergistically induce thrombopoietin production by hematopoietic cells."Int.J.Hematol.. 72. 455-462 (2001)
[Publications] Tsuji K.: "Expression of G-CSF receptor on myeloid progenitors."Leukemia and Lymphoma. (in press).
[Publications] Matsuoka S.: "CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages."Blood. 97. 419-425 (2001)
[Publications] Ma F.: "Cytokine requirement for the development of T-lineage potential from lymphohematopoietic progenitor cells."Br,J.Haematol.. (in press).
[Publications] Sugiyama.H.: "Peroxisome proliferator-activated receptors are expressed in human cultured mast cells : a possible role of these receptors in negative regulation of mast cell activation."Eur.J.Immunol.. (in press).
[Publications] Xu M.: "Evidence for the presence of primitive megakaryopoiesis in the early yolk sac."Blood. (in press).
[Publications] Ueda T.: "Hematopoietic capability of cord blood CD34^+ cells : a comparison with that of adult bone marrow CD34^+ cells."Int.J.Hoematol.. (in press).
[Publications] Yoshimasu T.: "Prompt and durable hematopoietic reconstitution by an unrelated cord blood transplantation in a child with Fanconi anemia."Bone Marrow Transplant.. (in press).
[Publications] Miyamoto K.: "Inhibitory effect of interleukin-3 on the early development of human B-lymphopoiesis."Br.J.Haematol.. (in press).
[Publications] Matsuoka S.: "Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleura by AGM region-derived stromal cells."Blood. (in press).
[Publications] Hisakawa H.: "Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryo expressing hGM-CSF receptors but not erythropoietin receptors."Blood. (in press).
[Publications] Ma F.: "Development of human lymphohematopoietic stem/progenitor cells defined by CD34 and CD81 expressions."Blood. (in press).
[Publications] 石井武文: "急性リンパ性白血病治療後期に発症したL-アスパラギナーゼによる壊死性膵炎"日小血会誌. 14. 328-332 (2000)
[Publications] 岩本彰太郎: "大量rhG-CSF療法中にmonosomy7を伴うMDSに移行したKostmann症候群"日小血会誌. 14. 338-345 (2000)
[Publications] 三牛哲夫: "造血幹細胞移植における支持療法と今後の課題"Biotherapy. 14. 292-300 (2000)
[Publications] 辻浩一郎: "増幅造血幹細胞移植ガイドライン"分子細胞療法. 1. 197-201 (2000)
[Publications] 海老原康博: "造血幹細胞の同定検査 2)コロニー法"検査と技術. 28. 971-972 (2000)
[Publications] 辻浩一郎: "造血幹細胞の起源と性状"医学のあゆみ. 194. 1021-1025 (2000)
[Publications] 杉山大介: "AGM領域"分子細胞療法. 1. 92-93 (2000)
[Publications] 辻浩一郎: "造血幹細胞の増幅"血液・免疫・腫瘍. (印刷中).
[Publications] 辻浩一郎: "試験管内造血幹細胞増幅"現代医療. (印刷中).
[Publications] 辻浩一郎: "造血幹細胞コロニー刺激因子と臍帯血造血幹細胞の体外増幅"日本産婦人科・新生児血液学会. (印刷中).
[Publications] Nakahata T.: "Cell Therapy"Springer-Verlag, Tokyo. 2 (2000)
[Publications] Nakahata T.: "Mast Cell Biology"Academic Press (in press).
[Publications] Tsuji K.: "Methods in Molecular Medicine-Cytokines and Colony Stimulating Factors"The Human Press (in press).
[Publications] 田中竜平: "造血器疾患治療マニュアル"メディカルレビュー社(大阪)(印刷中).
[Publications] 辻浩一郎: "小児の症候群"診断と治療社(東京)(印刷中).

2000 Fiscal Year Annual Research Report

サル胚性幹細胞からの器官特異的機能細胞の分化誘導法の開発

Principal Investigator

辻 浩一郎 東京大学, 医科学研究所, 助教授 (50179991)

Research Products

[Publications] Ueda T.: "Expansion of human NOD/SCID-repopulating cells by a combination of stem cell factor, Flk2/Flt3 ligand, thrombopoietin and a complex of interleukin-6 and soluble interleukin-6 receptor."J.Clin.Invest.. 105. 1013-1021 (2000)

[Publications] Hayashi Y.: "SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3."Cancer Res.. 60. 1139-1145 (2000)

[Publications] Ebihara Y.: "Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34^+ cells."Br.J.Haematol.. 109. 153-161 (2000)

[Publications] Ueda T.: "Hematopoietic repopulating ability of cord blood CD34^+ cells in NOD/Shi-scid mice."Stem Cells. 18. 204-213 (2000)

[Publications] Ueda T.: "Massive pericardial and pleural effusion with anasarca following allogeneic bone marrow transplantation."Int.J.Hematol.. 71. 394-397 (2000)

[Publications] Sato T.: "Erythroid progenitors differentiate and mature in response to endogenous erythropoietin."J.Clin.Invest.. 106. 263-270 (2000)

[Publications] Ishii T.: "Improvement in bronchiolitis obliterans organizing pneumonia by combination of oral predonisolone and low dose erythromycin in a child after allogegeneic bone marrow transplantation."Bone Marrow Transplant. 26. 907-910 (2000)

[Publications] Sugiyama H.: "Peroxisome proliferator-activated receptors are expressed in mouse bone marrow-derived mast cells."FEBS Lett.. 467. 259-262 (2000)

[Publications] Yoshino H.: "Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice."Bone Marrow Transplant.. 26. 1211-1216 (2000)

[Publications] Takaki S.: "Control of B cell production by the adaptor protein Lnk, a negative regulator of tyrosine kinase signaling."Immunity. 13. 599-609 (2000)

[Publications] Matsui A.: "gp130 and c-kit signals synergistically induce thrombopoietin production by hematopoietic cells."Int.J.Hematol.. 72. 455-462 (2001)

[Publications] Tsuji K.: "Expression of G-CSF receptor on myeloid progenitors."Leukemia and Lymphoma. (in press).

[Publications] Matsuoka S.: "CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages."Blood. 97. 419-425 (2001)

[Publications] Ma F.: "Cytokine requirement for the development of T-lineage potential from lymphohematopoietic progenitor cells."Br,J.Haematol.. (in press).

[Publications] Sugiyama.H.: "Peroxisome proliferator-activated receptors are expressed in human cultured mast cells : a possible role of these receptors in negative regulation of mast cell activation."Eur.J.Immunol.. (in press).

[Publications] Xu M.: "Evidence for the presence of primitive megakaryopoiesis in the early yolk sac."Blood. (in press).

[Publications] Ueda T.: "Hematopoietic capability of cord blood CD34^+ cells : a comparison with that of adult bone marrow CD34^+ cells."Int.J.Hoematol.. (in press).

[Publications] Yoshimasu T.: "Prompt and durable hematopoietic reconstitution by an unrelated cord blood transplantation in a child with Fanconi anemia."Bone Marrow Transplant.. (in press).

[Publications] Miyamoto K.: "Inhibitory effect of interleukin-3 on the early development of human B-lymphopoiesis."Br.J.Haematol.. (in press).

[Publications] Matsuoka S.: "Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleura by AGM region-derived stromal cells."Blood. (in press).

[Publications] Hisakawa H.: "Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryo expressing hGM-CSF receptors but not erythropoietin receptors."Blood. (in press).

[Publications] Ma F.: "Development of human lymphohematopoietic stem/progenitor cells defined by CD34 and CD81 expressions."Blood. (in press).

[Publications] 石井武文: "急性リンパ性白血病治療後期に発症したL-アスパラギナーゼによる壊死性膵炎"日小血会誌. 14. 328-332 (2000)

[Publications] 岩本彰太郎: "大量rhG-CSF療法中にmonosomy7を伴うMDSに移行したKostmann症候群"日小血会誌. 14. 338-345 (2000)

[Publications] 三牛哲夫: "造血幹細胞移植における支持療法と今後の課題"Biotherapy. 14. 292-300 (2000)

[Publications] 辻浩一郎: "増幅造血幹細胞移植ガイドライン"分子細胞療法. 1. 197-201 (2000)

[Publications] 海老原康博: "造血幹細胞の同定検査 2)コロニー法"検査と技術. 28. 971-972 (2000)

[Publications] 辻浩一郎: "造血幹細胞の起源と性状"医学のあゆみ. 194. 1021-1025 (2000)

[Publications] 杉山大介: "AGM領域"分子細胞療法. 1. 92-93 (2000)

[Publications] 辻浩一郎: "造血幹細胞の増幅"血液・免疫・腫瘍. (印刷中).

[Publications] 辻浩一郎: "試験管内造血幹細胞増幅"現代医療. (印刷中).

[Publications] 辻浩一郎: "造血幹細胞コロニー刺激因子と臍帯血造血幹細胞の体外増幅"日本産婦人科・新生児血液学会. (印刷中).

[Publications] Nakahata T.: "Cell Therapy"Springer-Verlag, Tokyo. 2 (2000)

[Publications] Nakahata T.: "Mast Cell Biology"Academic Press (in press).

[Publications] Tsuji K.: "Methods in Molecular Medicine-Cytokines and Colony Stimulating Factors"The Human Press (in press).

[Publications] 田中竜平: "造血器疾患治療マニュアル"メディカルレビュー社(大阪)(印刷中).

[Publications] 辻浩一郎: "小児の症候群"診断と治療社(東京)(印刷中).

辻浩一郎東京大学, 医科学研究所, 助教授 (50179991)