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The therapeutic efficacy of mouse ES cell derived cardiac progenitor cell transplantation in the ischemic heart

Research Project

Project/Area Number 16390394
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKyoto University

Principal Investigator

KOMEDA Masashi  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20303810)

Co-Investigator(Kenkyū-buntansha) IKEDA Tadashi  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (40281092)
NAKAHATA Tatutoshi  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20110744)
MATSUBARA Hiroaki  Kyoto Prefectural University of Medicine, Professor, 医学研究科, 教授 (10239072)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsES cell / cell transplantation / old myocardial infarction / myocardial regeneration / Flk1 / 慢性心筋梗塞 / FACS / 急性心筋梗塞 / 陳旧性心筋梗塞
Research Abstract

This study was to investigate and establish the procedure to proliferate and differentiate the mouse Flk1 positive ES cells to cardiac progenitor cells and cardiomyocytes. Then, cell transplantation was done to investigate the proliferation and differentiation of mouse Flk1 positive ES cells after implanted into ischemic myocardium and to check the improvement of cardiac function.
To investigate and establish the procedure to proliferate and differentiate the mouse Flk1 positive ES cells to cardiac progenitor cells and cardiomyocytes.
1) We established the procedure to differentiate and proliferate 3million cardiomyocytes from mouse Flk1 positive ES cells at single approach.
2) We established the procedure to differentiate and proliferate the 2million cardiac progenitor cells (FCV : Flk1 positive, CXCR4 positive, VE-Cadherin negative) from mouse ES cells, with the purity of 80% at single approach.
Cell transplantation study using these mouse ES cell derived cardiac cell line.
1) Flk1 positi … More ve cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model.
2) In the mouse acute myocardial infarction model, we transplanted Flk1 positive cardiomyocytes which derived from mouse ES cells. We identified the donor cells survivality, differentiation into cardiomyocytes, restrain the left ventricle dilatation after infarction, and increase the fractional shortening in this model.
3) We performed the old myocardial infarction model using immunodeficiency mouse. We tried the cell transplantation therapy, but it was too difficult to do the therapy, due to the excessive thinness of the infarcted muscle wall.
4) We performed the old myocardial infarction model using immunodeficiency rat. 4 weeks after the induction of myocardial infarction, we transplanted 1million cardiac progenitor cells from mouse Flk1 positive ES cell.
First, we examined the transplanted cells survival and differentiation.
2 weeks after cell transplantation, recipient rats were sacrificed and specimens were made. We confirmed a large mass of transplanted cells survivajity by GFP staining and the differentiation to cardiomyocytes.
We evaluated the effect of cell transplantation by checking the cardiac function such as echocardiography and cardiac catheterization. But, there was no apparent effect of improvement of cardiac function.
Now we increasing the number of this model, and rechecking the improvement of cardiac function Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (4 results)

All 2005 2004 Other

All Journal Article (4 results)

  • [Journal Article] Identification of cardiac stem cells with FLK1,CD31, and VE-cadherin expression during embryonic stem cell differentiation2005

    • Author(s)
      Iida M, Heike T, Yoshimoto M, Baba S, Doi H, Nakahata T
    • Journal Title

      FASEB J. 19

      Pages: 371-378

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro2004

    • Author(s)
      Umeda K, Heike T, Yoshimoto M, Shiota M, Nakatsuji N, Nakahata T et al.
    • Journal Title

      Development 131

      Pages: 1869-1879

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Flkl+Cardiac Stem/Progenitor Cells Derived from Embryonic stem Cells Improve Cardiac Function in a Dilated Cardiomyopathy Mouse Model.

    • Author(s)
      Shiro Baba, Toshio Heike, Momoko Yoshimoto, Katsutsugu Umeda, Hiraku Doi, Toru Iwasa, Xue Lin, Satoshi Matsuoka, Masashi Komeda, Tatsutoshi Nakahata
    • Journal Title

      Cardiovascular Research (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Flk1+ Cardiac Stem/Progenitor Cells Derived from Embryonic Stem Cells Improve Cardiac Function in a Dilated Cardiomyopathy Mouse Model.

    • Author(s)
      Shiro Baba, Toshio Heike, Momoko Yoshimoto, Katsutsugu Umeda, Hiraku Doi, Toru Iwasa, Xue Lin, Satoshi Matsuoka, Masashi Komeda, Tatsutoshi Nakahata
    • Journal Title

      Cardiovascular Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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