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ヒト臍帯血、成人骨髄血、胚性幹細胞に用いた幹細胞の可塑性の研究

Research Project

Project/Area Number 17045012
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe 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) 海老原 康博  東京大学, 医科学研究所, 助手 (40302608)
河崎 裕英  東京大学, 医科学研究所, 助手 (80278621)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsヒト胚性幹細胞(ES細胞) / 胎仔肝 / ストローマ細胞 / 多能性造血前駆細胞 / 混合コロニー形成細胞 / 肥満細胞 / 抗アレルギー薬 / 造血幹細胞 / 造血前駆細胞 / 赤血球 / 成人型ヘモグロビン
Research Abstract

ヒトES細胞の臨床応用、特にヒトES細胞由来薬理効果評価細胞、とりわけ抗アレルギー薬の効果判定のための肥満細胞の産生の可能性について検討した。
ヒトES細胞をマウス胎仔肝由来ストローマ細胞と共培養すると、培養10日目頃よりMix-CFCは産生された。そこで、培養14日目に採取されたMix-CFCを、SCF(stem cell factor)、FL(Flk2-Hgand)、IL(interleukin)-3、IL/6、G-CSF(granulocyte colony-stimulating factor)、EPO(erythropoietin)、TPO(thrombopoietin)等の種々のサイトカイン存在下で液体培養すると、赤血球系細胞、巨核球系細胞、顆粒球系細胞、肥満細胞等様々な血液細胞が産生された。特に、培養2週間後には、培養液中には多くの肥満細胞が出現したが、これらの肥満細胞の大部分はtryptase(+)chymase(-)のT型肥満細胞(粘膜型肥満細胞)であった。培養1ヶ月頃には、一部にはtryptase(+)chymase(+)のTC型肥満細胞(組織型肥満細胞)も認められたが、多くはT型肥満細胞のままであった。
一方、マウス胎仔肝由来ストローマ細胞と14日間共培養されたヒトES細胞をSCFなどのサイトカイン存在下で直接液体培養すると、培養1週間目にはtryptase(-)chymase(+)細胞が出現し、培養1ヶ月後にはその多くはtryptase(+)chymase(+)のTC型肥満細胞となった。
以上の結果から、胎生期における肥満細胞の発達には、多能性造血前駆細胞を介して肥満細胞が産生される経路の他に、早期にTC型組織型肥満細胞を産生する経路が存在する可能性が示唆され、ヒトES細胞は、抗アレルギー薬の効果判定のための肥満細胞の供給源となると考えられた。

Report

(2 results)
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (41 results)

All 2007 2006 2005 Other

All Journal Article (33 results) Book (7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Definitive hematopoiesis from endothelial cells in mouse embryo; A simple guidance.2006

    • Author(s)
      Sugiyama, D. et al.
    • Journal Title

      Trends. Cardiovas. Med. 16

      Pages: 45-49

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Allogeneic hematopoietic cell transplantation from alternative donors with a conditioning regimen of low-dose irradiation, fludarabine and cyclophosphamide in Fanconi anemia.2006

    • Author(s)
      Yabe H.et al.
    • Journal Title

      Br. J. Haematol. 134

      Pages: 208-212

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hematopoietic origins of fibroblasts : II. In vitro studies of fibroblasts, CFU-F and fibrocytes.2006

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

      Exp. Hematol. 34

      Pages: 219-229

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear : mesenchymal cells and fibrocytes.2006

    • Author(s)
      Lang, H. et al.
    • Journal Title

      J. Comp. Neurol. 496

      Pages: 187-201

    • Related Report
      2006 Annual Research Report
  • [Journal Article] An in vivo analysis of hematopoietic stem cell potential : hematopoietic origin of cardiac valve interstitial cells.2006

    • Author(s)
      Visconti, R.P. et al.
    • Journal Title

      Circ Res. 98

      Pages: 690-696

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hematopoietic origins of fibroblasts : I. In vivo studies of fibroblasts associated with solid tumors.2006

    • Author(s)
      LaRue, A.C.et al.
    • Journal Title

      Exp. Hematol. 34

      Pages: 208-218

    • Related Report
      2006 Annual Research Report
  • [Journal Article] JMMLに対するビスフォスフォネートの効果2006

    • Author(s)
      大塚欣敏 他
    • Journal Title

      血液・腫瘍科 52

      Pages: 97-103

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Embryonic stem cellの造血幹細胞移植への応用2006

    • Author(s)
      辻浩一郎
    • Journal Title

      今日の移植 19

      Pages: 51-58

    • Related Report
      2006 Annual Research Report 2005 Annual Research Report
  • [Journal Article] ヒトES細胞かちの血液細胞の産生2006

    • Author(s)
      辻浩一郎
    • Journal Title

      臨床血液 47

      Pages: 445-450

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dysregulation of granulocyte, erythrocyte and NK cell lineages in Fli-1 gene targeted mice.2005

    • Author(s)
      Masuya M, et al.
    • Journal Title

      Blood 105

      Pages: 95-102

    • Related Report
      2005 Annual Research Report
  • [Journal Article] RAS-blocking bisphosphonate zoledronic acid inhibits the abnormal proliferation and differentiation of juvenile myelomonocytic leukemia cells in vitro.2005

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

      Blood 106

      Pages: 3134-3141

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Definitive hematopoiesis from acetyl LDL incorporating endothelial cells in the mouse embryo.2005

    • Author(s)
      Sugiyama D, et al.
    • Journal Title

      Stem Cells and Development 14

      Pages: 687-696

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CD34+CD7+Leukemic Progenitor Cells May Be Involved in Maintenance and Clonal Evolution of Chronic Myeloid Leukemia.2005

    • Author(s)
      Kosugi N, et al.
    • Journal Title

      Clin Cancer Res 11

      Pages: 505-511

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia.2005

    • Author(s)
      Hasegawa D, et al.
    • Journal Title

      Br J Haematol 128

      Pages: 805-812

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Granulocyte/macrophage origin of glomerular mesangial cells.2005

    • Author(s)
      Abe T, et al.
    • Journal Title

      Int J Hematol 82

      Pages: 115-118

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ヒト胚性幹細胞からの血液産生と再生医療2005

    • Author(s)
      辻浩一郎
    • Journal Title

      日小血会誌 19

      Pages: 175-180

    • NAID

      10016462545

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 骨髄由来造血幹細胞2005

    • Author(s)
      辻浩一郎
    • Journal Title

      最新医学 60

      Pages: 1695-1700

    • Related Report
      2005 Annual Research Report
  • [Journal Article] B cell can be obtained from pre-circulatory yolk sac, but with low frequency.

    • Author(s)
      Sugiyama D. et al.
    • Journal Title

      Dev. Biol. (in press)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Novel method for efficient production of multipotential hematopoietic progenitors from human embryonic stem cells.

    • Author(s)
      Ma F.et al.
    • Journal Title

      Int J Haematol (in press)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 4-integrin endothelium derived from primate embryonic stem cells generates both primitive and definitive hematopoietic cells.

    • Author(s)
      Shinoda G. et al.
    • Journal Title

      Blood (in press)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Sequential analysis of α- and β-globin gene expression during erythropoietic differentiation from primate embryonic stem cells.

    • Author(s)
      Umeda K. et al.
    • Journal Title

      Stem Cells (in press)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 末梢血幹細胞

    • Author(s)
      辻浩一郎
    • Journal Title

      血液・腫瘍科 (印刷中)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] アフェレシスとがん治療

    • Author(s)
      辻浩一郎
    • Journal Title

      日本アフェレシス学会雑誌 (印刷中)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 造血幹細胞から赤血球ヘの分化

    • Author(s)
      辻浩一郎
    • Journal Title

      膜 (印刷中)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 人工血液

    • Author(s)
      辻浩一郎
    • Journal Title

      チャイルドヘルス (印刷中)(発行確定)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Definitive hematopoiesis from endothelial cells in mouse embryo ; A simple guidance.

    • Author(s)
      Sugiyama D, et al.
    • Journal Title

      Trends Cardiovas Med (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear : mesenchymal cells and fibrocytes.

    • Author(s)
      Lang H, et al.
    • Journal Title

      J Comp Neurol (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hematopoietic origins of fibroblasts : I. In vivo studies of fibroblasts associated with solid tumors.

    • Author(s)
      LaRue AC, et al.
    • Journal Title

      Exp Hematol (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hematopoietic origins of fibroblasts : II. In vitro studies of fibroblasts, CFU-F and fibrocytes.

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

      Exp Hematol (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] An In Vivo Analysis of Hematopoietic Stem Cell Potential. Hematopoietic Origin of Cardiac Valve Interstitial Cells.

    • Author(s)
      Visconti RP, et al.
    • Journal Title

      Circ Res. (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] JMMLに対するビスフォスフォネートの効果

    • Author(s)
      大塚欣敏, 他
    • Journal Title

      血液・腫瘍科 (印刷中)

    • Related Report
      2005 Annual Research Report
  • [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

      臨床血液 (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 末梢血幹細胞

    • Author(s)
      辻浩一郎
    • Journal Title

      血液・腫瘍科 (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Book] Annual Review呼吸器 20072007

    • Author(s)
      辻浩一郎
    • Total Pages
      242
    • Publisher
      中外医学社(東京)
    • Related Report
      2006 Annual Research Report
  • [Book] 新小児がんの診断と治療2007

    • Author(s)
      辻浩一郎
    • Total Pages
      367
    • Publisher
      診断と治療社(東京)
    • Related Report
      2006 Annual Research Report
  • [Book] よく理解できる子どものがん-診療から看護ケアまで-2006

    • Author(s)
      辻浩一郎
    • Total Pages
      346
    • Publisher
      永井書店(東京)
    • Related Report
      2006 Annual Research Report
  • [Book] 臍帯血移植の基礎と臨床

    • Author(s)
      辻浩一郎
    • Publisher
      医学書院(東京)(印刷中)(発行確定)
    • Related Report
      2006 Annual Research Report
  • [Book] よく理解できる子どものがん-診療から看護ケアまで-

    • Author(s)
      辻浩一郎
    • Publisher
      永井書店(印刷中)
    • Related Report
      2005 Annual Research Report
  • [Book] 臍帯血移植の基礎と臨床

    • Author(s)
      辻浩一郎
    • Publisher
      医学書院(印刷中)
    • Related Report
      2005 Annual Research Report
  • [Book] Annual Review呼吸器 2007

    • Author(s)
      辻浩一郎
    • Publisher
      中外医学社(印刷中)
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] Method of producing multipotential hematopoietic progenitors.2005

    • Inventor(s)
      Kohichiro Tsuji, Feng Ma
    • Industrial Property Rights Holder
      Kohichiro Tsuji, Feng Ma
    • Filing Date
      2005-10-19
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2018-03-28  

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