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Analysis of human innate immunity and acquired immune mechanism during fetal period using human ES cells

Research Project

Project/Area Number 24390272
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

MOCHIZUKI Shinji  東京大学, 医科学研究所, 特任助教 (90349473)

Co-Investigator(Kenkyū-buntansha) EBIHARA Yasuhiro  東京大学, 医科学研究所, 特任准教授 (40302608)
TSUJI Kohichiro  東京大学, 医科学研究所, 准教授 (50179991)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords胎児医学 / ES細胞 / 自然免疫
Outline of Final Research Achievements

We succeeded the production of human mast cells and eosinophils from hematopoietic cells derived human ES cells and established the system that reflect the generation and development of these immune cells in human embryo. It is indicated that they first develop connective tissue-type mast cells that both express chymase and tryptase at primary time of induction and then from multipotential hematopoietic progenitor cells at a comparatively later stage they develop mucosal mast cells. It is also suggested that eosinophils and basophils might be originated from common progenitor cells. We succeeded the production of human neutrophils from hematopoietic cells derived human iPS cells as well. In the analyses, they showed normal and healthy functions, compared with the one derived from iPS cells from patients of congenital neutrophilic disorders.
it is expected to be a useful tool for investigations into the mechanism of the generation of innate immune system and many diseases.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (39 results)

All 2015 2014 2013 2012 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 8 results) Presentation (20 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Screening of Drugs to Treat 8p11 Myeloproliferative Syndrome Using Patient-Derived Induced Pluripotent Stem Cells with Fusion Gene CEP110-FGFR12015

    • Author(s)
      Yamamoto S, Otsu M, Matsuzaka E, Konishi C, Takagi H, Hanada S, Mochizuki S, Nakauchi H, Imai K, Tsuji K, Ebihara Y
    • Journal Title

      PloS one

      Volume: 10 Issue: 3 Pages: e0120841-e0120841

    • DOI

      10.1371/journal.pone.0120841

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Third allogeneic stem cell transplantation (SCT) using unrelated cord blood for relapsed acute leukemia after second allogeneic SCT2015

    • Author(s)
      Konuma T, Kato S, Ooi J, Ebihara Y, Mochizuki S, Oiwa-Monna M, Tojo A, Takahashi S.
    • Journal Title

      International journal of hematology.

      Volume: 101 Issue: 4 Pages: 392

    • DOI

      10.1007/s12185-015-1755-7

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro expansion of CD34(+)CD38(-) cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia.2015

    • Author(s)
      Sakashita K, Kato I, Daifu T, Saida S, Hiramatsu H, Nishinaka Y, Ebihara Y, Ma F, Matsuda K, Saito S, Hirabayashi K, Kurata T, Uyen Lt, Nakazawa Y, Tsuji K, Heike T, Nakahata T, Koike K.
    • Journal Title

      Leukemia.

      Volume: 29(3) Issue: 3 Pages: 606-14

    • DOI

      10.1038/leu.2014.239

    • NAID

      120007110642

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies2014

    • Author(s)
      Konuma T, Tojo A, et al.
    • Journal Title

      Bone Marrow Transplant.

      Volume: 49 Issue: 5 Pages: 634

    • DOI

      10.1038/bmt.2014.10

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients2014

    • Author(s)
      Sakurai M, Kunimoto H, Watanabe N, Fukuchi Y, Yuasa S, Yamazaki S, Nishimura T, Sadahira K, Fukuda K, Okano H, Nakauchi H, Morita Y, Matsumura I, Kudo K, Ito E, Ebihara Y, Tsuji K, Harada Y, Harada H, Okamoto S, Nakajima H
    • Journal Title

      Leukemia

      Volume: 28 Issue: 12 Pages: 2344-54

    • DOI

      10.1038/leu.2014.136

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allogeneic stem cell transplantation for patients with acute myeloid leukemia developing from severe congenital neutropenia.2014

    • Author(s)
      Ebihara Y, Ishikawa K, Mochizuki S, Tanaka R, Manabe A, Iseki T, Maekawa T, Tsuji K.
    • Journal Title

      Br J Haematol.

      Volume: 164 Issue: 3 Pages: 451-464

    • DOI

      10.1111/bjh.12638

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-unit cord blood transplantation after granulocyte colony-stimulating factor-combined myeloablative conditioning for myeloid malignancies not in remission2014

    • Author(s)
      Konuma T, Tojo A, et al.
    • Journal Title

      Biol Blood Marrow Transplant. 20(3):

      Volume: 20 Issue: 3 Pages: 396

    • DOI

      10.1016/j.bbmt.2013.12.555

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of ABO blood group incompatibility on the outcome of single-unit cord blood transplantation after myeloablative conditioning2014

    • Author(s)
      Konuma T, Tojo A, et al.
    • Journal Title

      Biol Blood Marrow Transplant.

      Volume: 20 Issue: 4 Pages: 577

    • DOI

      10.1016/j.bbmt.2013.12.563

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function.2014

    • Author(s)
      Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
    • Journal Title

      PLos One

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1371/journal.pone.0087425

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pneumothorax in an early phase after allogeneic hematopoietic stem cell transplantation2013

    • Author(s)
      Ebihara Y, Tojo A, et al.
    • Journal Title

      Hematol Rep.

      Volume: 5 Issue: 2 Pages: 34

    • DOI

      10.4081/hr.2013.e10

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unusual extramedullary relapse after haploidentical bone marrow transplantation in a patient with acute lymphoblastic leukemia.2013

    • Author(s)
      Ebihara Y, Yamamoto S, Mochizuki S, Tsukada M, Taya Y, Sato A, Kawakita T, Kato S, Ooi J, Takahashi S, Tojo A, Tsuji K.
    • Journal Title

      J Blood Disorders Transf

      Volume: 4 Issue: 05 Pages: 155-155

    • DOI

      10.4172/2155-9864.1000155

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Feasibility of autologous bone marrow mesenchymal stem ceels cultured with autologous serum for treatment of hemophilic arthropathy.2013

    • Author(s)
      Ebihara Y, et al.
    • Journal Title

      Haemophilia

      Volume: 19

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia-derived pluipotent stem cells with heterozygous ELANE mutation.2013

    • Author(s)
      Hiramoto T
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110 Issue: 8 Pages: 3023-3028

    • DOI

      10.1073/pnas.1217039110

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multidimensional role of CD34 protein in hematopoietic stem cell biology.2013

    • Author(s)
      Singh VK, et al.
    • Journal Title

      Int J Sci Tech Man

      Volume: (in press)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of red blood cells from human embryonic/induced pluripotent stem cells for blood transfusion.2012

    • Author(s)
      Ebihara Y, et al.
    • Journal Title

      Int J Hematol.

      Volume: 95 Issue: 6 Pages: 610-616

    • DOI

      10.1007/s12185-012-1107-9

    • NAID

      10030793386

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute lymphoblastic leukemia with t(1;19)(q23Ip13)/TCF3-PBX1 fusion in an adult male with Down syndrome.2012

    • Author(s)
      Yamamoto S, et al.
    • Journal Title

      Acta Haematol.

      Volume: 128 Pages: 242-243

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] JPLSG ALL-R08-I観察研究高リスク群(S3/4)における中間解析結果2014

    • Author(s)
      植木 英亮, 小川 千登世, 西 眞範, 望月 慎史, 後藤 裕明, JPLSG再発ALL委員会早期再発解析ワーキンググループ
    • Organizer
      日本小児血液・がん学会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] RCCに対して同種臍帯血移植を施行した2例2014

    • Author(s)
      海老原 康博, 望月 慎史, 大津 真, 辻 浩一郎
    • Organizer
      日本小児血液・がん学会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 重症先天性好中球減少症患者由来のiPS細胞の樹立とその分子生物学的解析2013

    • Author(s)
      海老原康博、平本貴史、山本将平、望月慎史、辻浩一郎、溝口洋子、中村和洋、小林正夫
    • Organizer
      第116回日本小児科学会
    • Place of Presentation
      広島:広島国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] Drug screening for the 8p11 myeloproliferative syndrome using patient iPS cells2013

    • Author(s)
      Mai Nanya, Shohei Yamamoto, Yasuhiro Ebihara, Shinji Mochizuki, Makoto Otsu, Minoru Tozuka, Hiromitsu Nakauchi, Kohichiro Tsuji
    • Organizer
      第75回日本血液学会
    • Place of Presentation
      札幌:ロイトン札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Generation and analysis of a novel model for CMML with acquired expression of CBL Q367P2013

    • Author(s)
      Yuichiro Nakata,Takeshi Ueda,Norimasa Yamasaki,Akiko Nagamachi,Keiyo Takubo,Yasuhiro Ebihara,Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji,Toshio Suda,Toshiya Inaba, Hiroaki Honda
    • Organizer
      第75回日本血液学会
    • Place of Presentation
      札幌:ロイトン札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒトiPS由来肥満細胞の機能解析2013

    • Author(s)
      五十嵐晃、熊谷智明、平井博之、永田欽也、花田佐智代、 海老原康博、辻浩一郎
    • Organizer
      第63回日本アレルギー学会
    • Place of Presentation
      東京:ホテルニューオータニ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 自己骨髄由来間葉系幹細胞を用いた血友病関節症に対する治療の可能性2013

    • Author(s)
      海老原康博、望月慎史、大津真、竹谷英之、辻浩一郎
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡:ヒルトン福岡シーホーク
    • Related Report
      2013 Annual Research Report
  • [Presentation] 本邦におけるボルテゾミブ併用化学療法を行った小児再発難治性急性リンパ性白血病 24 例 の後方視的検討2013

    • Author(s)
      望月慎史、小川千登世、佐野秀樹、木下明俊、篠田邦大、宮下恵実子、吉原宏樹、井口晶裕、吉田咲子、西川拓朗、西眞範、豊田秀実、熊本忠史、中村和洋、西内律雄、菊田敦、後藤裕明、足立壮一、水谷修紀
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡:ヒルトン福岡シーホーク
    • Related Report
      2013 Annual Research Report
  • [Presentation] 同種骨髄移植後に発症したair leak syndromeの2例2013

    • Author(s)
      海老原康博, 他
    • Organizer
      第35回日本造血細胞移植学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] Suppressed neutrophi1 development in hematopoiesis of induced pluripotent stem cells derived from a severe congenital neutropenia patient with ELA2 mutation.2012

    • Author(s)
      Takafumi Hiramoto, et al.
    • Organizer
      東大生命科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-06-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] 重症先天性好中球減少症患者由来のiPS細胞の樹立とその解析2012

    • Author(s)
      海老原康博, 他
    • Organizer
      第115回日本小児科学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 重症先天性好中球減少症患者由来iPS細胞の遺伝子発現の検討 重症先天性好中球減少症患者由来iPS細胞の樹立とその解析 : 第2報2012

    • Author(s)
      平本貴史, 他
    • Organizer
      第33回日本炎症・再生医学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Suppressed neutrophil development in hematopoiesis of induced pluripotent stem cells derived from a severe congenital neutropenia patient with ELA2 mutation.2012

    • Author(s)
      Takafumi Hiramoto, et al.
    • Organizer
      ISSCR meeting
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] 同種骨髄移植後に発症したair leak syndromeの2例2012

    • Author(s)
      海老原康博, 他
    • Organizer
      第45回日本小児呼吸器疾患科学会
    • Place of Presentation
      旭川
    • Related Report
      2012 Annual Research Report
  • [Presentation] Refractory 8pll myeloproliferative syndrome : a case report2012

    • Author(s)
      Shohei Yamamoto, et al.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impaired hematopoietic differentiation of iPSCs derived from apatientwi th FPD/AML2012

    • Author(s)
      Masatoshi Sakurai, et al.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] Acquired expression of c-Cbl Q367P mutation induces myeloid cell proliferation2012

    • Author(s)
      Yuichiro Nakata, et al.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] A20, a ubiquitin-modifying enzyme for NF-kappaB, plays an importantrole in normal hematopoiesis2012

    • Author(s)
      Akiko Nagaraachi, et al.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] 治療抵抗性8q11骨髄増殖症候群の1例2012

    • Author(s)
      山本将平, 他
    • Organizer
      第54回日本小児血液・がん学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impaired Hematopoietic Differentiation of iPSCs Derived From Patients with FPD/AML2012

    • Author(s)
      Masatoshi Sakurai, et al.
    • Organizer
      ASH meeting
    • Place of Presentation
      Atlanta, U.S.A.
    • Related Report
      2012 Annual Research Report
  • [Book] 遺伝子医学MOOK(1349-2527)27号2015

    • Author(s)
      海老原 康博
    • Total Pages
      8
    • Publisher
      メディカル ドゥ
    • Related Report
      2014 Annual Research Report
  • [Book] 臍帯血移植の基礎と臨床2013

    • Author(s)
      辻浩一郎
    • Publisher
      医学書院
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://stemcell-u-tokyo.org/scp/

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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