New Strategy of Platelet Transfusion Independent of Donor Blood

2011 Fiscal Year Final Research Report

• Project/Area Number: 21300160
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Kyoto University (2011); The University of Tokyo (2009-2010)
• Principal Investigator: ETO Koji 京都大学, ips細胞研究所, 教授 (50286986)
• Project Period (FY): 2009 – 2011
• Keywords: 再生医工学 / 人工臓器工学

Research Abstract

This research program enabled to establish the methodology of induction of'megakaryocyte cell line' from human embryonic stem(ES) cells or induced pluripotent stem(iPS) cells, contributing to the huge amount of platelet generation in vitro. We also developed new drug to block the platelet inactivation occurred at 37°C through the inhibition of ADAM10 and ADAM17. The program of the development of new device for platelet production from megakaryocytes based upon'shear stress theory' enabled the

Research Products

• [Journal Article] In vitro generation of megakaryocytes and platelets from human embryonic stem cells and induced pluripotent stem cell (2012)
  • Author(s): Takayama N, Eto K
  • Journal Title: Methods Mol Biol Volume: 788 Pages: 205-17
• [Journal Article] Integrinαvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells. Blood (2012)
  • Author(s): Umemoto T, Yamato M, Ishihara J, Shiratsuchi Y, Utsumi M, Morita Y, Tsukui H, Terasawa M, Shibata T, Nishida K, Kobayashi Y, Petrich BG, Nakauchi H, Eto K, Okano T.
  • Journal Title: Blood Volume: 119(1) Pages: 83-94
• [Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling (2012)
  • Author(s): Nishimura S, Manabe I, Nagasaki M, Kakuta S, Iwakura Y, Takayama N, Ooehara J, Otsu M, Kamiya A, Petrich B, Urano T, Kadono T, Sato S, Aiba A, Yamashita H, Sugiura S, Kadowaki T, Nakauchi H, Eto K, Nagai R.
  • Journal Title: Blood Volume: 119(8) Pages: 45-56
• [Journal Article] Heterozygous ITGA2B R995W mutation inducing constitutive activation of the{alpha} IIb{beta} 3 receptor affects proplatelet formation and causes congenital macro thrombocytopenia (2011)
  • Author(s): Kunishima S, Kashiwagi H, Otsu M, Takayama N, Eto K, Onodera M, Miyajima Y, Takamatsu Y, Suzumiya J, Matsubara K, Tomiyama Y, Saito H.
  • Journal Title: Blood Volume: 117 Pages: 5479-84
• [Journal Article] Reduction of N-Glycolylneuraminic Acid in Human Induced Pluripotent Stem Cells Generated or Cultured under Feeder-and Serum-Free Defined Conditions (2010)
  • Author(s): Hayashi Y, Chan T, Warashina M, Fukuda M, Ariizumi T, Okabayashi K, Takayama N, Otsu M, Eto K, Furue MK, Michiue T, Ohnuma K, Nakauchi H, Asashima M.
  • Journal Title: Plops One Volume: 5 Pages: 14099
• [Journal Article] Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells (2010)
  • Author(s): Takayama N, Nishimura S, Nakamura S, Shimizu T, Ohnishi R, Endo H, Yamaguchi T, Otsu M, Nishimura K, Nakanishi M, Sawaguchi A, Nagai R, Takahashi K, Yamanaka S, Nakauchi H, Eto K.
  • Journal Title: J Exp Med Volume: 207 Pages: 2817-30
• [Journal Article] Essential in vivo roles of the c-type lectin receptor CLEC-2 : Embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconnections and impaired thrombus formation of CLEC-2-deficient platelets (2010)
  • Author(s): Suzuki-Inoue K, Inoue O, Ding G, Nishimura S, Hokamura K, Eto K, Kashiwagi H, Tomiyama Y, Yatomi Y, Umemura K, Shin Y, Hirashima M, Ozaki Y.
  • Journal Title: J Biol Chem Volume: 285 Pages: 24494-507
• [Journal Article] Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo (2010)
  • Author(s): Takizawa H, Nishimura S, Takayama N, Oda A, Nishikii H, Morita Y, Kakinuma S, Yamazaki S, Okamura S, Tamura N, Goto S, Sawaguchi A, Manabe I, Takatsu K, Nakauchi H, Takaki S, Eto K.
  • Journal Title: J Clin Invest Volume: 120 Pages: 179-90
• [Journal Article] Evidence that integrin alpha IIb beta 3-dependent interaction of mast cells with fibrinogen exacerbates chronic inflammation (2009)
  • Author(s): Oki T, Eto K, Izawa K, Yamanishi Y, Inagaki N, Frampton J, Kitamura T, Kitaura J.
  • Journal Title: J Biol Chem Volume: 284 Pages: 31463-72
• [Journal Article] Definitive proof for direct reprogramming of hematopoietic cells to pluripotency (2009)
  • Author(s): Okabe M, Otsu M, Ahn DH, Kobayashi T, Wakiyama Y, Morita Y, Onodera M, Eto K, Ema H, Nakauchi H
  • Journal Title: Blood Volume: 114 Pages: 1764-7
• [Journal Article] CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity (2009)
  • Author(s): Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R.
  • Journal Title: Nat Med Volume: 15 Pages: 914-20
• [Journal Article] The actin polymerization regulator WAVE2 is required for early bone marrow repopulation by hematopoietic stem cells (2009)
  • Author(s): Ogaeri T, Eto K, Otsu M, Ema H, Nakauchi H.
  • Journal Title: Stem Cells Volume: 27 Pages: 1120-9
• [Presentation] ES Cells and iPS Cells for Cardiovascular Research (2012)
  • Author(s): Eto K, Gary Lyons, Andre Terzic.
  • Organizer: American Heart Association SCIENTIFIC SESSIONS 2010
  • Place of Presentation: (Chicago, USA) Invited Speaker(Session)
  • Year and Date: 20121113-17
• [Presentation] Blood generation from iPS cells toward clinical applications (2011)
  • Author(s): Eto K.
  • Organizer: 第32回日本炎症・再生医学会1st Meeting of Asian-Pacific Federation of Inflammation and Regeneration合同開催
  • Place of Presentation: (Kyoto, JAPAN.) Invited Speaker
  • Year and Date: 20110602-03
• [Presentation] Epigenetic Memory Enables the Dominant Generation of Adult-Type Erythrocytes From Human Induced Pluripotent Stem Cells (2010)
  • Author(s): Takayama N, Sano S, Shimizu T, Kawahata R, Endo H, Nakamura S, Ogawa S, Nakauchi H, Eto K.
  • Organizer: 52st American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: (Orlando, USA) Oral
  • Year and Date: 20101204-07
• [Presentation] Generation of Monoclonal TCR-Expressing Human T-Lineage Lymphocytes From Induced Pluripotent Stem Cells of Signal Peripheral T-Lymphocyte Origin (2010)
  • Author(s): Nishimura T, Kaneko S, Gotoh H, Takayama N, Shimizu T, Iriguchi S, Tajima Y, Yasui Y, Watanabe N, Takahashi S, Eto K, Nakauchi H.
  • Organizer: 52st American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: (Orlando, USA) Oral
  • Year and Date: 20101204-07
• [Presentation] Novel Target of Ex Vivo Expansion ; Integrinαvβ3 Ligation Enables Regulation of Hematopoietic Stem Cell Division Leading to Maintenance of Reconstitution Potential (2010)
  • Author(s): Eto K.
  • Organizer: The 1st ISCT Asia-Pacific Regional Meeting
  • Place of Presentation: (Miyazaki, Japan.) Invited Speaker
  • Year and Date: 20101017-20
• [Presentation] Human Induced Pluripotent Stem Cell-derived Blood Cells toward Clinical Application (2010)
  • Author(s): Eto K.
  • Organizer: The 1st ISCT Asia-Pacific Regional Meeting
  • Place of Presentation: (Miyazaki, Japan.) Invited Speaker
  • Year and Date: 20101017-20
• [Presentation] Generation of engraft able hematopoietic stem cells from teratomas formed by an injection of induced pluripotent stem cells (2010)
  • Author(s): Suzuki N, Yamazaki S, Yamaguchi T, Takaki S, Eto K, Nakauchi H.
  • Organizer: International Society for Stem Cell Research 8th Annual Meeting(ISSCR)
  • Place of Presentation: (San Francisco, USA) Oral Session
  • Year and Date: 20100616-19
• [Presentation] Feeder and serum free culture of human induced pluripotent stem cells (2010)
  • Author(s): Chan T, Hayashi Y, Takayama N, Otsu M, Eto K, Furue-Kusuda M, Ohnuma K, Nakauchi H, Asashima M.
  • Organizer: International Society for Stem Cell Research 8th Annual Meeting(ISSCR)
  • Place of Presentation: (San Francisco, USA) Poster Session
  • Year and Date: 20100616-19
• [Presentation] Monoclonal guidance of T Lineage lymphocytes from human induced pluripotent stem cells originating from a single peripheral T Lymphocyte (2010)
  • Author(s): Nishimura T, Kaneko S, Gotoh H, Takayama N, Nakamura S, Shimizu T, Iriguchi S, Tachikawa-Kawana A, Takahashi S, Watanabe N, Otsu M, Eto K, Nakauchi H.
  • Organizer: International Society for Stem Cell Research 8th Annual Meeting(ISSCR)
  • Place of Presentation: (San Francisco, USA) Poster Session
  • Year and Date: 20100616-19
• [Presentation] CD61 is involved in thrombopoietin-mediated maintenance of mouse hematopoietic stem cells (2010)
  • Author(s): Umemoto T, Yamato M, Shiratsuchi Y, Utsumi M, Terasawa M, Morita Y, Nishida K, Kobayashi Y, Petrich Brian G, Ginsberg Mark H, Nakauchi H, Eto K, Okano T.
  • Organizer: International Society for Stem Cell Research 8th Annual Meeting(ISSCR)
  • Place of Presentation: (San Francisco, USA) Poster Session
  • Year and Date: 20100616-19
• [Presentation] Novel in vivo imaging enables single-cell-level evaluation of the functionality of platelets derived from human induced pluripotent stem cells (2010)
  • Author(s): Nishimura S, Takayama N, Otsu M, Nakamura S, Ohnishi R, Endo H, Nagai R, Nakauchi H, Eto K.
  • Organizer: International Society for Stem Cell Research 8th Annual Meeting(ISSCR)
  • Place of Presentation: (San Francisco, USA) Poster Session
  • Year and Date: 20100616-19
• [Presentation] Human iPS cells from Blood and Blood from iPS cells (2010)
  • Author(s): Eto K.
  • Organizer: Hematopoiesis in Health and Disease in Lund
  • Place of Presentation: (Lund, Sweden.) Invited Speaker
  • Year and Date: 20100515-17
• [Presentation] Cancellation of c-MYC Silencing in Human Induced Pluripotent Stem Cells Contributes to the Efficient in Vitro Production of Platelets with the Ability of Hemostasis In Vino (2009)
  • Author(s): Takayama N, Nakamura S, Nishimura S, Ohnishi R, Takahashi K, Yamanaka S, Eto K, and Nakauchi H.
  • Organizer: 51st American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: (New Orleans, USA) Poster Session
  • Year and Date: 20091205-08
• [Presentation] CD61/Integrinβ3 Ligation Contributes to the Thrombopoietin-Mediated Niche Function of Mouse Hematopoietic Stem Cells (2009)
  • Author(s): Umemoto T, Yamato M, Shiratsuchi Y, Tsukada K, Utsumi M, Morita Y, Terasawa M, Shibata T, Nishida K, Kobayashi Y, Petrich Brian G, Ginsberg Mark H, Nakauchi H, Eto K, and Okano T.
  • Organizer: 51st American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: (New Orleans, USA) Speaker
  • Year and Date: 20091205-08
• [Presentation] NOVEL THERAPEUTIC STRATEGY IN PATIENTS WHO REQUIRE REPEATED TRANSFUSION OF HUMAN LEUKOCYTE ANTIGEN-MATCHED PLATELETS DERIVED FROM HUMAN INDUCED PLURIPOTENT STEM CELLS (2009)
  • Author(s): Eto K.
  • Organizer: XXth REGIONAL CONGRESS, ASIA
  • Place of Presentation: (Nagoya, JAPAN.) Invited Speaker
  • Year and Date: 20091114-18
• [Presentation] NOVEL THERAPEUTIC STRATEGY IN PATIENTS WHO REQUIRE REPEATED TRANSFUSION OF HUMAN LEUKOCYTE ANTIGEN-MATCHED PLATELETS DERIVED FROM HUMAN IPS CELLS (2009)
  • Author(s): Takayama N, Eto K, Nakamura S, Ohnishi R, Yamanaka S, Nakauchi H.
  • Organizer: International Society for Stem Cell Research 7th Annual Meeting(ISSCR)
  • Place of Presentation: (Barce Session lona, Spain.) Poster Seccion
  • Year and Date: 20090608-11
• [Remarks]
  • URL: http://www.cira.kyoto-u.ac.jp/j/research/eto_summary.html
• [Remarks]
  • URL: http://www.cira.kyoto-u.ac.jp/eto/
• [Patent(Industrial Property Rights)] 多能性幹細胞からの巨血球及び/又は血小板の製造方法 (2011)
  • Inventor(s): 西野泰斗、中村隆典、岩本俊介、江藤浩之、辻嘉代子、中内啓光
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 特許、特願2011-108253
  • Filing Date: 2011-05-13
  • Overseas
• [Patent(Industrial Property Rights)] 血小板の機能を維持するための組成物 (2011)
  • Inventor(s): 江藤浩之、大西椋子、中内啓光、村田隆彦
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 特許、PCT/JP2011/071190
  • Filing Date: 2011-09-16
  • Overseas
• [Patent(Industrial Property Rights)] 多能性幹細胞からの血液細胞分化に関する培養方法 (2011)
  • Inventor(s): 佐野進弥、江藤浩之、高山直也、中内啓光
  • Industrial Property Rights Holder: 国立大学法人東京大学テルモ株式会社
  • Industrial Property Number: 特許、PCT/JP2011/070563
  • Filing Date: 2011-09-09
  • Overseas
• [Patent(Industrial Property Rights)] 血小板産生方法及び血小板産生装置 (2011)
  • Inventor(s): 江藤浩之、中内啓光、福田敏男、高松遼、新井史人
  • Industrial Property Rights Holder: 国立大学法人東京大学国立大学法人名古屋大学
  • Industrial Property Number: 特許、特願2011-143383
  • Filing Date: 2011-06-28
  • Overseas
• [Patent(Industrial Property Rights)] 血小板産生の場構築の為の巨核球細胞の多核化の促進法 (2011)
  • Inventor(s): 江藤浩之、中内啓光、高山直也、中村壮
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 特許、特願2011-108253
  • Filing Date: 2011-05-13
  • Overseas
• [Patent(Industrial Property Rights)] ES細胞からの造血前駆細胞を内包する構造物、及び該構造物を用いた血球細胞の調製法 (2011)
  • Inventor(s): 中内啓光、江藤浩之、高山直也、錦井秀和、津久井弘子
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: PCT/JP2007/001081/WO2008/41370
  • Filing Date: 2011-11-15
  • Overseas