Analysis of the development of fetal hematopoiesis using embryonicstem cell

• Project/Area Number: 19591277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: EBIHARA Yasuhiro The University of Tokyo, 医科学研究所, 助教 (40302608)
• Co-Investigator(Kenkyū-buntansha): 辻 浩一郎 東京大学, 医科学研究所, 准教授 (50179991)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ヒトES細胞 / 胎生期造血 / 胎児肝 / ストローマ細胞 / CD34+細胞 / CD45+細胞 / GPA+細胞 / 造血前駆細胞 / ヒト胚性幹細胞(ES細胞) / 赤血球造血 / 胎児型ヘモグロビン(HbF) / 成人型ヘモグロビン(HbA) / αグロビン / βグロビン / γグロビン

Research Abstract

ヒト胎生期の造血発達の解明を目的として、胎生期の未分化な多能性幹細胞であるヒト胚性幹細胞(ES 細胞)から血液細胞への分化を再現することを試みた。そのためには、胎生期の造血環境を実験的に再構築することが重要と考えた。そこで、哺乳類の胎生期造血は肝臓で劇的に増幅するため、マウス胎仔の肝臓の造血環境を反映するストローマ細胞を樹立し、ES 細胞と共培養したところ、血液細胞へ分化誘導することに成功した。

Research Products

• [Journal Article] Identification and clinicalapplication of fibroblasts/myofibroblastsderived from hematopoietic stem cells (2008)
  • Author(s): Ebihara Y.
  • Journal Title: Japan J Pediatr Hematol 22 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Direct development of functionally maturetryptase/ chymase double positive (2008)
  • Author(s): Ma F, Tsuji K(他13名、13番目)
  • Journal Title: tissue-type mast cells from primate EScells. Stem Cells 26 Pages: 706-714
  • Peer Reviewed
• [Journal Article] Generation of functional erythrocytesfrom human embryonic stem cell-derived (2008)
  • Author(s): Ma F, Ebihara Y, Tsuji K(他8名、2番目)
  • Journal Title: definitive hematopoiesis. Proc Natl AcadSci USA 105 Pages: 13087-13092
  • Peer Reviewed
• [Journal Article] Homeostatic erythropoiesis by thetranscription factor IRF2 through (2008)
  • Author(s): Mizutani T, Tsuji K, Ebihara Y(他3名、3番目)
  • Journal Title: attenuation of type I interferon signaling.Exp Hematol 41 Pages: 255-264
  • Peer Reviewed
• [Journal Article] Cardiovascular toxicity ofcryopreserved cord blood cell infusion (2008)
  • Author(s): Konuma T, Ebihara Y, Tsuji K(他5名、10番目)
  • Journal Title: Bone Marrow Transplant 41 Pages: 861-865
  • Peer Reviewed
• [Journal Article] 造血幹細胞由来線維芽細胞および筋線維芽細胞の同定とその臨床応用 (2008)
  • Author(s): 海老原康博
  • Journal Title: 日本小児血液学会会誌 22 Pages: 1-6
  • NAID: 10025700202
  • Peer Reviewed
• [Journal Article] 胎児造血とヒトES細胞からの血液の産生 (2008)
  • Author(s): 辻浩一郎
  • Journal Title: 日本小児科学会雑誌 112 Pages: 1654-1662
  • NAID: 10024842380
• [Journal Article] Identification and clinical application of fibroblasts/myofibroblasts derived from hematopoietic stem cells. (2008)
  • Author(s): Ebihara Y
  • Journal Title: Japan J Pediatr Hematol. 22 Pages: 1-6
  • NAID: 10025700202
  • Peer Reviewed
• [Journal Article] Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis. (2008)
  • Author(s): Ma F et al.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 13087-13092
  • Peer Reviewed
• [Journal Article] Direct development of functionally mature tryptase/ chymase double, positive tissue-type mast cells from primate ES cells. (2008)
  • Author(s): Ma F et al.
  • Journal Title: Stem Cells 26 Pages: 706-714
  • Peer Reviewed
• [Journal Article] Homeostatic erythropoiesis by the transcription factor HtF2-threnigh attenuation of type I interferon signaling. (2008)
  • Author(s): Mizutani T et al.
  • Journal Title: Exp Hematol 36 Pages: 255-264
  • Peer Reviewed
• [Journal Article] Cardiovascular toxicity of cryopreserved cord blood cell infusion. (2008)
  • Author(s): Konuma T et al.
  • Journal Title: Bone Marrrow Transplant 41 Pages: 861-865
  • Peer Reviewed
• [Journal Article] 胎児造血とヒトES細胞からの血液の産生 (2008)
  • Author(s): 辻浩一郎
  • Journal Title: 日本小児科学寒雑誌 112 Pages: 1654-1662
  • NAID: 10024842380
• [Journal Article] Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling (2008)
  • Author(s): Mizutani T
  • Journal Title: Exp Hematol (掲載確定)
  • Peer Reviewed
• [Journal Article] Direct development of functionally mature tryptase/ chymase double positive tissue-type mast cells from primate ES cells (2008)
  • Author(s): Ma F
  • Journal Title: Stem Cells (掲載確定)
  • Peer Reviewed
• [Journal Article] Cardiovascular toxicity of cryopreserved cord blood cell infusion. (2008)
  • Author(s): Konuma T
  • Journal Title: Bone Marrrow Transplant (掲載確定)
  • Peer Reviewed
• [Journal Article] Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis (2008)
  • Author(s): Ma F
  • Journal Title: Proc Natl Acad Sci USA (掲載確定)
  • Peer Reviewed
• [Journal Article] B cell can be obtained frompre-circulatory yolk sac, but with lowfrequency (2007)
  • Author(s): Kulkeaw K, Tsuji K(他4名、5番目)
  • Journal Title: Dev Biol 301 Pages: 53-61
  • Peer Reviewed
• [Journal Article] Novel method for efficientproduction of multipotential (2007)
  • Author(s): Ma F, Wang D, Hanada S, Ebihara Y, Tsuji K(他4名、4番目)
  • Journal Title: hematopoietic progenitors from humanembryonic stem cells. Int J Hematol 85 Pages: 371-379
  • Peer Reviewed
• [Journal Article] The effect of donor leukocyte infusion(DLI) on refractory pure red blood cell aplasiaafter allogeneic stem cell transplantation ina patient with myelodysplastic syndromedeveloping from Kostmann syndrome. (2007)
  • Author(s): Ebihara Y, Manabe A, Tsuji K(他6名、1番目)
  • Journal Title: Int J Hematol 86 Pages: 446-450
  • Peer Reviewed
• [Journal Article] 末梢血幹細胞 (2007)
  • Author(s): 辻浩一郎
  • Journal Title: 血液・腫瘍科 55(Suppl.5) Pages: 15-19
• [Journal Article] がん治療とアフェレシス (2007)
  • Author(s): 辻浩一郎
  • Journal Title: 日本アフェレシス学会雑誌 26 Pages: 226-227
• [Journal Article] 造血幹細胞から赤血球への分化膜 (2007)
  • Author(s): 辻浩一郎
  • Journal Title: 32 Pages: 155-162
  • Peer Reviewed
• [Journal Article] 人工血液 (2007)
  • Author(s): 辻浩一郎
  • Journal Title: チャイルドヘルス 10 Pages: 42-43
• [Journal Article] B cell can be obtained from pre-circulatory yolk sac, but with low frequency. (2007)
  • Author(s): Sugiyama D,
  • Journal Title: Dev Biol 301 Pages: 53-61
  • Peer Reviewed
• [Journal Article] Novel method fbr efficient production of multipotential hematopoietic progenitors from human embryonic stem cells (2007)
  • Author(s): Ma F
  • Journal Title: Int J Hematol 85 Pages: 371-379
  • Peer Reviewed
• [Journal Article] The effect of donor leukocyte infusion (DLI) on refractory pure red blood cell aplasia after allogeneic stem cell transplantation in a patient with myelodysplastic syndrome developing from Kostmann syndrome. (2007)
  • Author(s): Ebihara Y
  • Journal Title: Int J Hematol 86 Pages: 446-450
  • Peer Reviewed
• [Journal Article] 末梢血幹細胞 (2007)
  • Author(s): 辻浩一郎
  • Journal Title: 血液・腫瘍科 55(Supp1.5) Pages: 15-19
• [Journal Article] 造血幹細胞から赤血球への分化 (2007)
  • Author(s): 辻浩一郎
  • Journal Title: 膜 32 Pages: 155-162
  • Peer Reviewed
• [Journal Article] 造血幹細胞由来線維芽細胞および筋線維芽細胞の同定とその臨床応用 (2007)
  • Author(s): 海老原康博
  • Journal Title: 日小血会誌 22 Pages: 1-6
  • NAID: 10025700202
  • Peer Reviewed
• [Journal Article] Application of whole mouse embryo
  • Author(s): Kulkeaw K, Tsuji K(他4名、5番目)
  • Journal Title: culture system on stem cell research. StemCell Rev & Rep
  • Peer Reviewed
• [Journal Article] ヒトES細胞からの血液細胞の産生
  • Author(s): 辻浩一郎
  • Journal Title: 人工血液
• [Journal Article] iPS 細胞からの血液誘導臨床検査
  • Author(s): 辻浩一郎
• [Journal Article] Application of whole mouse embryo culture system on stem cell research.
  • Author(s): Kulkeaw K et al.
  • Journal Title: Stem Cell Rev & Rep (掲載確定)
  • Peer Reviewed
• [Journal Article] ヒ卜ES細胞からの血液細胞の産生
  • Author(s): 辻浩一郎
  • Journal Title: 人工血液 (掲載確定)
• [Journal Article] iPS細胞からの血液誘導
  • Author(s): 辻浩一郎
  • Journal Title: 臨床検査 (掲載確定)
• [Presentation] ヒトES細胞維持能を有するヒトES細胞由来ストローマ細胞 (2009)
  • Author(s): 海老原康博、馬峰、花田佐智代、富澤大輔、辻浩一郎、小野田春男、小柳津直樹
  • Organizer: 第8回日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-05
• [Presentation] 15-20歳の思春期症例に対する臍帯血移植の検討 (2009)
  • Author(s): 海老原康博、辻浩一郎、佐藤亜紀、加藤せい子、門間文彦、小沼貴晶、塚田信弘、大井淳、高橋聡、東條有伸、浅野茂隆
  • Organizer: 第31回日本造血細胞移植学会
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-05
• [Presentation] 15-20歳の思春期症例に対する騎帯血移植の検討 (2009)
  • Author(s): 海老原康博 他
  • Organizer: 第31回躰造細胞移植学会
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-05
• [Presentation] Myelodysplastic Syndrome(MDS) and Myeloproliferative Disease (MPD) in Children : A prospective Resistration of 222 Cases. (2008)
  • Author(s): S. Hirabayashi, A. Manabe, S. Watanabe,Y. Zaike, M. Tsuchida, Masunaga A, A.Yoshimi, M. Ito, A. Kikuchi, K. Tsuji, A.Ohara, S. Kojima, T. Nakahata.
  • Organizer: 15th annual meeting of AmericanSociety of Hematology
  • Place of Presentation: SanFrancisco, USA
  • Year and Date: 2008-12-07
• [Presentation] Myelodysplastic Syndrome (MDS) and Myeloproliferative Disease (MPD) in Children: A prospective Resistration of 222 Cases. (2008)
  • Author(s): Hirabayashi S et al.
  • Organizer: 15th annual meeting of American Society of Hematology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-07
• [Presentation] 異種動物血清を用いないヒトembryonic stem cell(hESC)から間葉系幹細胞(MSC)への分化 (2008)
  • Author(s): 海老原康博 他
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] Differential production ofconnective tisue-type and mucosal mastcells from human embryonic stem cells foranti-allergy drug screening, st (2008)
  • Author(s): Tsuji K
  • Organizer: International Conference on Drug Design &Discovery
  • Place of Presentation: dubai
  • Year and Date: 2008-02-07
• [Presentation] Differential production of connective tisue-type and mucosal mast cells from human embryonic stem cells for anti-allergy drug (2008)
  • Author(s): Tsuji K
  • Organizer: 1st International Conference on Drug Design & Discovery
  • Place of Presentation: dubai
  • Year and Date: 2008-02-07
• [Presentation] 異種動物血清を用いないヒトembryonic stem cell(hESC)から間葉系幹細胞(MSC)への分化誘導 (2008)
  • Author(s): 海老原康博、馬峰、花田佐智代、辻浩一郎、小野田春雄、小柳津直樹
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都
• [Presentation] Clonal analysis of progressivematuration of erythroid cells from humanembryonic stem cell-derived definitivehematopoiesis. 49th annual meeting of (2007)
  • Author(s): Ebihara Y, Umeda K, Sakai H, Hanada S,Zhang H, Tsuchida E, Nakahata T, NakauchiH, Tsuji K
  • Organizer: American Society of Hematology
  • Place of Presentation: atlanta
  • Year and Date: 2007-12-09
• [Presentation] Clonal analysis of progressive maturation of erythroid cells from human embryonic stem cell-derived definitive hematopoiesis (2007)
  • Author(s): Ma F
  • Organizer: 49th annual meeting of American Society of Hematology
  • Place of Presentation: atlanta
  • Year and Date: 2007-12-09
• [Presentation] 小児MDSのセントラルレビュー435例の解析 (2007)
  • Author(s): 真部淳、土田昌宏、在家裕司、増永敦子、菅原祥子,吉美礼美、伊藤雅文、辻浩一郎、菊地陽、中畑龍俊
  • Organizer: 日本血液学会2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-13
• [Presentation] 小児MDSのセントラルレビュー435例の解析 (2007)
  • Author(s): 真部淳
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-13
• [Presentation] ヒトES細胞から血液細胞への分化誘導 (2007)
  • Author(s): 馬峰、海老原康博、中畑龍俊、中内啓光、辻浩一郎
  • Organizer: 日本血液学会2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
• [Presentation] IRES によるAML1発現は胎生期における末梢血管形成および二次造血に必須である (2007)
  • Author(s): 本田浩章、馬峰、小川秀明、山崎憲政、奥田司、辻浩一郎、宮崎和子
  • Organizer: 日本血液学会2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
• [Presentation] ヒトES細胞から血液細胞への分化誘導 (2007)
  • Author(s): 馬峰
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
• [Presentation] IRESによるAML1発現は胎生期における末梢血管形成および二次造血に必須である (2007)
  • Author(s): 本田浩章
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
• [Presentation] eneration of human embryonic stemcell-derived erythroid cells withfunctional maturity 36th Annualscientific meeting of International (2007)
  • Author(s): Ma F, Ebihara Y, Hanada S, Sakai H,Tsuchida E, Nakahata T, Nakauchi H, TsujiK
  • Organizer: Society of Experimental Hematology
  • Place of Presentation: humberg
  • Year and Date: 2007-09-30
• [Presentation] Generation of human embryonic stem cell-derived erythroid cells with functional maturity (2007)
  • Author(s): Ma F
  • Organizer: 36th Annual scientific meeting of International Society of Experimental Hematology
  • Place of Presentation: humberg
  • Year and Date: 2007-09-30
• [Book] 臍帯血移植の基礎と臨床 (2008)
  • Author(s): 辻浩一郎
  • Publisher: 医学書院(掲載確定)
• [Book] 幹細胞をめぐる現状と展望Annual Review 呼吸器 2007(工藤翔二, 土屋了介, 金沢実, 大田健) (2007)
  • Author(s): 辻浩一郎
  • Total Pages: 246
  • Publisher: 中外医学社
• [Book] 遺伝子治療新小児がんの診断と治療(別所文雄, 杉本徹, 横森欣司) (2007)
  • Author(s): 辻浩一郎
  • Total Pages: 374
  • Publisher: 診断と治療社
• [Book] Annual Review呼吸器 2007 (2007)
  • Author(s): 辻浩一郎
  • Total Pages: 246
  • Publisher: 中外医学社
• [Book] 新小児がんの診断と治療 (2007)
  • Author(s): 辻浩一郎
  • Total Pages: 374
  • Publisher: 診断と治療社
• [Remarks] 東京大学医科学研究所ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/
• [Remarks] (by Asian-PacificInternational Molecular Biology Network)Highlights : "Turning stem cells intoBlood", on 17 December 2008
  • URL: http://www.natureasia.com/A-IMBN/article.php?id=168A-IBMNRearch
• [Remarks] A-IBMN Rearch (by Asian-Pacific International Molecular Biology Network) Highlights: "Turning stem cells into Blood", on 17 December 2008.
  • URL: http://www.natureasia.com/A-IMBN/article.php?id=168
• [Remarks] 東京大学医科学研究所ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/