1996 Fiscal Year Annual Research Report

単細胞レベルでのヒト造血幹細胞の自己複製と分化増殖機構の解析

Research Project

Project/Area Number	08670856
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)
Keywords	ヒト造血幹細胞 / CD34陽性細胞 / 単細胞培養 / IL-6受容体 / トロンボポエチン
Research Abstract	1.ヒト造血幹細胞/前駆細胞におけるIL-6受容体(IL-6R)の発現と分化能の単細胞レベルでの解析ヒト造血幹細胞/前駆細胞分画であるCD34+細胞をIL-6Rの発現の有無で分画し、CD34+/IL-6R+細胞とCD34+/IL-6R-細胞を各々単細胞培養すると、前者からは顆粒球・マクロファージコロニーが形成されただけであったが、後者からは顆粒球・マクロファージコロニーに加えて赤芽球バースト、巨核球コロニー、混合コロニーが形成された。さらに、CD34+/IL-6R-細胞はCD34+/IL-6+細胞と比較して、多数のlong-term culture-initiating cellを含んでいた。以上の結果より、CD34+/IL-6R-細胞はCD34+/IL-6R+細胞より未分化な分画に属すると考えられた。 2.ヒト造血幹細胞/前駆細胞のトロンボポエチン(TPO)に対する反応性の単細胞レベルでの解析従来TPOは巨核球系細胞に特異的に作用するサイトカインと考えられていた。しかし、CD34+細胞を単細胞分離し、TPO存在下で1週間単細胞培養すると、未分化な造血細胞から成る芽球コロニーが形成される。さらにこの単細胞由来の芽球コロニーに種々の造血因子を添加すると、巨核球のみならず、顆粒球、マクロファージ、赤血球などが産生された。この結果は、TPOは巨核球系細胞のみならず、未分化な造血幹細胞/前駆細胞にも作用することを示唆すると考えられた。

Research Products

(26 results)

All Other

All Publications (26 results)

[Publications] "Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous lcukemia in serum-free culture" Exp.Hematol.24. 116-122 (1996)
[Publications] Okumura N.: "Chemotactic and chemokinetic activity of stem cell factor on murine hematopoietic progenitor cells" Blood. 87. 4100-4108 (1996)
[Publications] Tanaka R.: "Characterization of peripheral blood progenitor cells(PBPC) mobilized by filgrostim (rHuG-CSF) in normal volunteers:Dose-effect relationship for filgrastim with the characte of mobilized PBPC." Br.J.Haematol.92. 795-803 (1996)
[Publications] Sui X.: "Erythropoietin-independent erythrocyte production:signals through gp130 and c-kit dramatically promote erythropoiesis from human CD34+ cells" J.Exp.Med.183. 837-845 (1996)
[Publications] Nakahata T.: "Role of gp130 and c-kit signalings in the proliferation and differentiation of human homopoietic progenitor cells" Cancer Chemother.Pharmacol.38(Suppl). S64-68 (1996)
[Publications] Saito H.: "Selective growth of human mast cells induced by Steel factor,IL-6,and prostaglandin E2 from cord blood mononuclear cells" J.Immunol.157. 343-350 (1996)
[Publications] Tajima S.: "Analysis of IL-6 receptor and gp130 expressions and proliferative capability of human CD34+ cells" J.Exp.Med.184. 1357-1364 (1996)
[Publications] Muraoka K.: "Defective response to thrombopoietin and impaired expression of c-mpl mRNA in bone marrow cells in congenital amegakaryocytic thrombocytopen" Br.J.Haematol.(in press).
[Publications] Sui X.: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis from human CD34^+ cells through gp130 signaling" Blood. (in press).
[Publications] Nakahata T.: "Ex vivo expansion of human primitive hemopoietic progenitors" Stem Cells. (in press).
[Publications] Tsuji K.: "Role of soluble interleukin-6 receptor with interleukin-6 in human hematopoiesis" Hematology. (in press).
[Publications] Nichijima I.: "Hematopoietic and lymphcpoietic responses in human GM-CSF receptor transgenic mice injected with human GM-CSF" Blood. (in press).
[Publications] Yoshida M.: "Thrombopoietin alone stimulates the early proliferation and survival of human erythroid,myeloid and multipotential progenitors in serwm-free culture" Br.J.Haematol.(in press).
[Publications] Muraoka K.: "Thrombopoietin-independent effect of interferon-γ on the proliferation of human megakaryocyte progenitors" Br.J.Haematol.in press.
[Publications] 辻浩一郎: "マスト細胞とサイトカイン" アレルギーの領域. 3. 39-43 (1996)
[Publications] 辻浩一郎: "c-kitを発現する細胞とその機能" アレルギー科. 1. 420-427 (1996)
[Publications] 辻浩一郎: "幹細胞のin vitro増幅" 臨床血液. 37. 579-583 (1996)
[Publications] 辻浩一郎: "造血幹細胞の増殖因子" 臨床免疫. 29. 134-140 (1996)
[Publications] 辻浩一郎: "造血幹細胞の増殖幅" 臨床検査. 40. 901-905 (1996)
[Publications] 辻浩一郎: "造血幹細胞の動員とその機序" 医学のあゆみ. (印刷中).
[Publications] 辻浩一郎: "造血幹細胞の増幅と幹細胞移植" 細胞. (印刷中).
[Publications] Nakahata T.: "Bone marrow Transplantation-Basic and Clinical Studies" Springer-Verlag, 17 (1996)
[Publications] 辻浩一郎: "疾病とサイトカイン-病因から治療への応用まで" 真興交易医書(印刷中),
[Publications] 辻浩一郎: "小児科学" 医学書院(印刷中),
[Publications] 辻浩一郎: "血液内科学" 中外医学社(印刷中),
[Publications] 辻浩一郎: "内科学教科書" 文光堂(印刷中),

1996 Fiscal Year Annual Research Report

単細胞レベルでのヒト造血幹細胞の自己複製と分化増殖機構の解析

Principal Investigator

辻 浩一郎 東京大学, 医科学研究所, 助教授 (50179991)

Research Products

[Publications] "Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous lcukemia in serum-free culture" Exp.Hematol.24. 116-122 (1996)

[Publications] Okumura N.: "Chemotactic and chemokinetic activity of stem cell factor on murine hematopoietic progenitor cells" Blood. 87. 4100-4108 (1996)

[Publications] Tanaka R.: "Characterization of peripheral blood progenitor cells(PBPC) mobilized by filgrostim (rHuG-CSF) in normal volunteers:Dose-effect relationship for filgrastim with the characte of mobilized PBPC." Br.J.Haematol.92. 795-803 (1996)

[Publications] Sui X.: "Erythropoietin-independent erythrocyte production:signals through gp130 and c-kit dramatically promote erythropoiesis from human CD34+ cells" J.Exp.Med.183. 837-845 (1996)

[Publications] Nakahata T.: "Role of gp130 and c-kit signalings in the proliferation and differentiation of human homopoietic progenitor cells" Cancer Chemother.Pharmacol.38(Suppl). S64-68 (1996)

[Publications] Saito H.: "Selective growth of human mast cells induced by Steel factor,IL-6,and prostaglandin E2 from cord blood mononuclear cells" J.Immunol.157. 343-350 (1996)

[Publications] Tajima S.: "Analysis of IL-6 receptor and gp130 expressions and proliferative capability of human CD34+ cells" J.Exp.Med.184. 1357-1364 (1996)

[Publications] Muraoka K.: "Defective response to thrombopoietin and impaired expression of c-mpl mRNA in bone marrow cells in congenital amegakaryocytic thrombocytopen" Br.J.Haematol.(in press).

[Publications] Sui X.: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis from human CD34^+ cells through gp130 signaling" Blood. (in press).

[Publications] Nakahata T.: "Ex vivo expansion of human primitive hemopoietic progenitors" Stem Cells. (in press).

[Publications] Tsuji K.: "Role of soluble interleukin-6 receptor with interleukin-6 in human hematopoiesis" Hematology. (in press).

[Publications] Nichijima I.: "Hematopoietic and lymphcpoietic responses in human GM-CSF receptor transgenic mice injected with human GM-CSF" Blood. (in press).

[Publications] Yoshida M.: "Thrombopoietin alone stimulates the early proliferation and survival of human erythroid,myeloid and multipotential progenitors in serwm-free culture" Br.J.Haematol.(in press).

[Publications] Muraoka K.: "Thrombopoietin-independent effect of interferon-γ on the proliferation of human megakaryocyte progenitors" Br.J.Haematol.in press.

[Publications] 辻 浩一郎: "マスト細胞とサイトカイン" アレルギーの領域. 3. 39-43 (1996)

[Publications] 辻 浩一郎: "c-kitを発現する細胞とその機能" アレルギー科. 1. 420-427 (1996)

[Publications] 辻 浩一郎: "幹細胞のin vitro増幅" 臨床血液. 37. 579-583 (1996)

[Publications] 辻 浩一郎: "造血幹細胞の増殖因子" 臨床免疫. 29. 134-140 (1996)

[Publications] 辻 浩一郎: "造血幹細胞の増殖幅" 臨床検査. 40. 901-905 (1996)

[Publications] 辻 浩一郎: "造血幹細胞の動員とその機序" 医学のあゆみ. (印刷中).

[Publications] 辻 浩一郎: "造血幹細胞の増幅と幹細胞移植" 細胞. (印刷中).

[Publications] Nakahata T.: "Bone marrow Transplantation-Basic and Clinical Studies" Springer-Verlag, 17 (1996)

[Publications] 辻 浩一郎: "疾病とサイトカイン-病因から治療への応用まで" 真興交易医書(印刷中),

[Publications] 辻 浩一郎: "小児科学" 医学書院(印刷中),

[Publications] 辻 浩一郎: "血液内科学" 中外医学社(印刷中),

[Publications] 辻 浩一郎: "内科学教科書" 文光堂(印刷中),

辻浩一郎東京大学, 医科学研究所, 助教授 (50179991)

[Publications] 辻浩一郎: "マスト細胞とサイトカイン" アレルギーの領域. 3. 39-43 (1996)

[Publications] 辻浩一郎: "c-kitを発現する細胞とその機能" アレルギー科. 1. 420-427 (1996)

[Publications] 辻浩一郎: "幹細胞のin vitro増幅" 臨床血液. 37. 579-583 (1996)

[Publications] 辻浩一郎: "造血幹細胞の増殖因子" 臨床免疫. 29. 134-140 (1996)

[Publications] 辻浩一郎: "造血幹細胞の増殖幅" 臨床検査. 40. 901-905 (1996)

[Publications] 辻浩一郎: "造血幹細胞の動員とその機序" 医学のあゆみ. (印刷中).

[Publications] 辻浩一郎: "造血幹細胞の増幅と幹細胞移植" 細胞. (印刷中).

[Publications] 辻浩一郎: "疾病とサイトカイン-病因から治療への応用まで" 真興交易医書(印刷中),

[Publications] 辻浩一郎: "小児科学" 医学書院(印刷中),

[Publications] 辻浩一郎: "血液内科学" 中外医学社(印刷中),

[Publications] 辻浩一郎: "内科学教科書" 文光堂(印刷中),