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Basic and clinical research for the application of "Ex vivo expanded erythroblast transplantation"

Research Project

Project/Area Number 17590714
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNiigata University

Principal Investigator

TOBA Ken  Niigata University, Medical and Dental Hospital, Lecturer, 医歯学総合病院, 講師 (60313540)

Co-Investigator(Kenkyū-buntansha) KATO Kiminori  Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (00303165)
HANAWA Haruo  Niigata University, Institute of Medicine and Dentistry, Lecturer, 医歯学系, 講師 (40282983)
AIZAWA Yoshifusa  Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (50143780)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsAngiogenesis / Erythroblasts / Erythropoietin / Ex vivo expansion / Cell Therapy
Research Abstract

Autologous bone marrow cell implantation (BMI) has been utilized for the treatment of limb ischemia, however the mechanism of angiogenesis by the therapy is not well known. As large as 500 to 1,000 mL of bone marrow collection is usually required for the treatment. The aim of this study was to develop a sophisticated cell therapy by using ex vivo cell culture technique.
In the beginning, we studied the mechanism of angiogenesis by BMI. We expected that the angiogenesis by the therapy mimicked the constitutional angiogenesis in the bone marrow tissue. Several angiogenic factors were strongly produced by erythroblasts. In vitro angiogenesis of HUVEC was conducted by erythroid colonies but not by myeloid colonies prepared from human blood stem cells. Erythroid cells in bone marrow played essential roles for angiogenesis in mouse limb ischemia model. In the in vivo model, simultaneous administration of erythropoietin with BMI enhanced angiogenesis presumably through surviving effect on erythroid cells extramedullary.
Next, we developed an ex vivo expansion system of erythroid cells from bone marrow stem cells. As the results, only 1 mL of bone marrow was enough to produce angiogenic factor producing cells that were fully compatible with 500 to 1,000 mL of freshly harvested bone marrow. The ex vivo expanded erythroblasts also expressed strong angiogenic effect in the mouse limb ischemic model.
A phase I/II trial of "Ex vivo expanded autologous erythroblast transplantation for the treatment of the patients with limb ischemia (EVEETA)" has been approved by the ethical committee and the IRB in the hospital. Cell culture for the clinical use will be enforced in the GMP-grade Cell Processing Center (CPC) in the hospital.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (38 results)

All 2006 2005

All Journal Article (36 results) Book (2 results)

  • [Journal Article] Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limbischemia-a case report.2006

    • Author(s)
      Ozawa T, Kato K, Sanada H, et al.
    • Journal Title

      Angiology 57・2

      Pages: 235-239

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.2006

    • Author(s)
      Ozawa T, Toba K, Kato K, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology 40・5

      Pages: 629-638

    • NAID

      120006735349

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cardioprotective effects of recombinant human erythropoietin in rats with experimental autoimmune myocarditis.2006

    • Author(s)
      Mitsuma W, Ito M, Toba K, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 344・3

      Pages: 987-994

    • NAID

      120006735347

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.2006

    • Author(s)
      Watanabe N, Narita M, Toba K, et al.
    • Journal Title

      Cytotherapy 8・2

      Pages: 118-129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hydrodynamic-Based Delivery of an Interleukin-22-Ig Fusion Gene Ameliorates Experimental Autoimmune Myocarditis in Rats.2006

    • Author(s)
      Chang H, Hanawa H, Toba K, et al.
    • Journal Title

      Journal of Immunology 177・6

      Pages: 3635-3643

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 末梢動脈疾患に対する細胞治療における工夫-末梢単核球移植追加治療とエリスロポエチン併用治療について-2006

    • Author(s)
      加藤公則, 鳥羽健, 相澤義房
    • Journal Title

      日本アフェレシス学会雑誌 25・3

      Pages: 210-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 骨髄単核細胞移植を用いた血管新生療法の作用機序とエリスロポエチンの臨床応用2006

    • Author(s)
      加藤公則, 鳥羽健, 小田雅人
    • Journal Title

      脈管学 46・5

      Pages: 595-601

    • NAID

      10020297811

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.2006

    • Author(s)
      Ozawa T, Toba K, Kato K, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology 40-5

      Pages: 629-638

    • NAID

      120006735349

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cardioprotective effects of recombinant human erythropoietin in rats with experimental autoimmune myocarditis.2006

    • Author(s)
      Mitsuma W, Ito M, Toba K, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 344-3

      Pages: 987-994

    • NAID

      120006735347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.2006

    • Author(s)
      Watanabe N, Narita M, Toba K, et al.
    • Journal Title

      Cytotherapy 8-2

      Pages: 118-129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hydrodynamic-Based Delivery of an Interleukin-22-Ig Fusion Gene Ameliorates Experimental Autoimmune Myocarditis in Rats.2006

    • Author(s)
      Chang H, Hanawa H, Toba K, et al.
    • Journal Title

      Journal of Immunology 177-6

      Pages: 3635-3643

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Therapeutic angiogenesis by bone marrow cell implantation in combination with peripheral blood cell implantation and erythropoietin.2006

    • Author(s)
      Kato K, Toba K, Aizawa Y.
    • Journal Title

      Japanese Journal of Apheresis 25-3

      Pages: 210-216

    • NAID

      110009721476

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mechanism of the angiogenesis by bone marrow implantation, and an application of erythropoietin for angiogenic therapy.2006

    • Author(s)
      Kato K, Toba K, Oda M et al.
    • Journal Title

      Journal of Japanese College of angiology 46-5

      Pages: 595-601

    • NAID

      10020297811

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limb ischemia-a case report.2006

    • Author(s)
      Ozawa T, Kato K, Sanada H, et al.
    • Journal Title

      Angiology 57・2

      Pages: 235-239

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.2006

    • Author(s)
      Ozawa T, Toba K, Kato K. et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology 40・5

      Pages: 629-638

    • NAID

      120006735349

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cardioprotective effects of recombinant human erythropoietin in rats with experimental autoimmune myocarditis.2006

    • Author(s)
      Mitsuma W, Ito M, Taba K. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 344・3

      Pages: 987-994

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Type I IFN-mediated enhancement o anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.2006

    • Author(s)
      Watanabe N, Narita M, Toba K, et al.
    • Journal Title

      Cytotherapy 8・2

      Pages: 118-129

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 抹消動脈疾患に対する細胞治療における工夫-抹消単核球移植追加治療とエリスロポエチン併用治療について-2006

    • Author(s)
      加藤公則, 鳥羽健, 相澤義房
    • Journal Title

      日本アフェレシス学会雑誌 25・3

      Pages: 210-216

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 骨髄単核細胞移植を用いた血管新生治療の作用機所とエリスロポエチンの臨床応用2006

    • Author(s)
      加藤公則, 鳥羽健, 小田雅人, 他
    • Journal Title

      脈管学 46・5

      Pages: 595-601

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.2006

    • Author(s)
      Ozawa, T
    • Journal Title

      J Mol Cell Cardiol (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells.2005

    • Author(s)
      Seki Y, Toba K, Fuse I, Sato N, et al.
    • Journal Title

      Thrombosis Research 115・3

      Pages: 219-228

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of hydrodynamics-based gene delivery of plasmid DNA encoding interleukin-1 receptor antagonist-Ig for treatment of rat autoimmune myocarditis : possible mechanism for lymphocytes and noncardiac cells.2005

    • Author(s)
      Liu H, Hanawa H, Yoshida T, Toba K, et al.
    • Journal Title

      Circulation 111・13

      Pages: 1593-1600

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Persistence of various chromosomal aberrations in recipient cells during complete remission after bone marrow transplantation followed by graft rejection.2005

    • Author(s)
      Masuko M, Furukawa T, Toba K, et al.
    • Journal Title

      Leukemia Research 29・9

      Pages: 1083-1087

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism.2005

    • Author(s)
      Elnaggar R, Hanawa H, Toba K, et al.
    • Journal Title

      European Journal of Immunology 35・6

      Pages: 1995-2005

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.2005

    • Author(s)
      Yoshida T, Hanawa H, Toba K, et al.
    • Journal Title

      Cardiovascular Research 68・2

      Pages: 278-288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells.2005

    • Author(s)
      Seki Y, Toba K, Fuse I, Sato N, et al.
    • Journal Title

      Thrombosis Research 115-3

      Pages: 219-228

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of hydrodynamics-based gene delivery of plasmid DNA encoding interleukin-1 receptor antagonist-Ig for treatment of rat autoimmune myocarditis : possible mechanism for lymphocytes and noncardiac cells.2005

    • Author(s)
      Liu H, Hanawa H, Yoshida T, Toba K, et al.
    • Journal Title

      Circulation 111-13

      Pages: 1593-1600

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Persistence of various chromosomal aberrations in recipient cells during complete remission after bone marrow transplantation followed by graft rejection.2005

    • Author(s)
      Masuko M, Furukawa T, Toba K, et al.
    • Journal Title

      Leukemia Research 29-9

      Pages: 1083-1087

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism.2005

    • Author(s)
      Elnaggar R, Hanawa H, Toba K, et al.
    • Journal Title

      European Journal of Immunology 35-6

      Pages: 1995-2005

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.2005

    • Author(s)
      Yoshida T, Hanawa H, Toba K, et al.
    • Journal Title

      Cardiovascular Research 68-2

      Pages: 278-288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limb ischemia-a case report.2005

    • Author(s)
      Ozawa T, Kato K, Sanada H, et al.
    • Journal Title

      Angiology 57-2

      Pages: 235-239

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells.2005

    • Author(s)
      Seki, Y
    • Journal Title

      Thromb Res 115・3

      Pages: 219-228

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of hydrodynamics-based gene delivery of plasmid DNA encoding interleukin-1 receptor antagonist-Ig for treatment of rat autoimmune myocarditis :possible mechanism for lymphocytes and noncardiac cells.2005

    • Author(s)
      Liu, H
    • Journal Title

      Circulation 111・13

      Pages: 1593-1600

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Persistance pf various chromosomal aberrations in recipient cells during complete remission after bone marrow transplantation followed by graft rejection.2005

    • Author(s)
      Masuko, M
    • Journal Title

      Leuk Res 29・9

      Pages: 1083-1087

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism.2005

    • Author(s)
      Elnaggar, R
    • Journal Title

      Eur J Immunol 35・6

      Pages: 1995-2005

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.2005

    • Author(s)
      Yoshida, T
    • Journal Title

      Cardiovasc Res 68・2

      Pages: 278-288

    • Related Report
      2005 Annual Research Report
  • [Book] エリスロポエチンのすべて2005

    • Author(s)
      鳥羽健
    • Total Pages
      293
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 「エリスロポエチンのすべて」第IV章-3「血管新生」2005

    • Author(s)
      鳥羽 健
    • Total Pages
      9
    • Publisher
      株式会社メディカルレビュー社
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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