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Development of innovative regenerative medicine for pediatric heart diseases using human ES cell and gene therapy technology

Research Project

Project/Area Number 17591126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKagoshima University (2006)
Kurume University (2005)

Principal Investigator

KOSAI Kenichiro  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院医歯学総合研究科, 教授 (90258418)

Co-Investigator(Kenkyū-buntansha) MAENO Yasuki  Kurume University, School of Medicine, Assistant Professor, 医学部, 講師 (90248401)
TAKEMURA Genzou  Gifu University, Graduate School of Medicine, Assistant Professor, 大学院医学研究科, 講師 (40283311)
KUNISADA Takahiro  Gifu University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (30205108)
TAKAHASHI Tomoyuki  Kurume University, School of Medicine, Associate Professor, 医学部, 助教授 (20332687)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsRegenerative medicine / Gene / Development and differentiation / Transplantation
Research Abstract

We obtained the following results from the present research that established human ES cell-based technologies of regenerative medicine for pediatric diseases.
1. The development of cardiac differentiation
(1) Addition of growth factors in combination with embryoid body formation led to efficient cardiac differentiation of mouse ES cells. However, this method did not work well in the case of using human ES cells. Therefore, we move to another method.
(2) We screened several kinds of mesenchymal cells, and found that coculture with certain two types of mesenchymal cells led to successful cardiac differentiation of not only mouse ES cells but also human ES cells.
(3) We generated plasmid vectors that expressed cardiac-specific transcriptional factors, and transduced either of these to mouse ES cells. However, this method did not result in drastically efficient induction of cardiac differentiation. The results indicates that cardiac-specific transcriptional factors are not the master gene.
2. Purification of the ES cell-derived cardiac cells
We applied gene therapy vector technologies to in vitro differentiation systems using mouse ES cells, and developed novel method that efficiently isolated ES cell-derived target cells. Then, we introduce this method to human ES cell system, however, unexpectedly, this system did not visualize the target cells. After our careful studies, we found that the unknown characters of human ES cells that were different from mouse ES cells.

Report

(2 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • Research Products

    (40 results)

All 2006 2005 Other

All Journal Article (29 results) Book (8 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Identification and isolation of embryonic stem cell-derived target cells by adenoviral conditional targeting.2006

    • Author(s)
      Takahashi T
    • Journal Title

      Melecular Therapy 14・5

      Pages: 673-683

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell cycle-specific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy : A promising implication of telomerase-dependent targeting cancer gene therapy.2006

    • Author(s)
      Murofushi Y
    • Journal Title

      International Journal of Oncology 29・3

      Pages: 681-688

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genetic modification of hepatocytes towards hepatocyte transplantation and liver tissue engineering.2006

    • Author(s)
      Kuge H
    • Journal Title

      Cell Transplant 15・1

      Pages: 1-12

    • 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] In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice : A comparative study to HGF.2006

    • Author(s)
      Khai NC
    • Journal Title

      Journal of Hepatology 44・6

      Pages: 1046-1054

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bone marrow-derived myocyte-like cells and regulation of repair-related cytokines after bone marrow cell transplantation.2006

    • Author(s)
      Misao Y
    • Journal Title

      Cardiovascular Research 69・2

      Pages: 476-490

    • 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] Hepatocyte growth factor gene therapy slows down the progression of diabetic nephropathy in db/db mice.2006

    • Author(s)
      Kagawa T
    • Journal Title

      Nephron Physiology 102・3-4

      Pages: 92-102

    • 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] Identification and isolation of embryonic stem cell-derived target cells by adenoviral conditional targeting.2006

    • Author(s)
      Takahashi T
    • Journal Title

      Molecular Therapy 14(5)

      Pages: 673-683

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell cycle-specific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy : A promising implication of telomerase-dependent targeting cancer gene therapy.2006

    • Author(s)
      Murofushi Y
    • Journal Title

      International Journal of Oncology. 29(3)

      Pages: 681-688

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genetic modification of hepatocytes towards hepatocyte transplantation and liver tissue engineering.2006

    • Author(s)
      Kuge H
    • Journal Title

      Cell Transplantation. 15(1)

      Pages: 1-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice : A comparative study to HGF2006

    • Author(s)
      Khai NC
    • Journal Title

      Journal of Hepatology. 44(6)

      Pages: 1046-1054

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bone marrow-derived myocyte-like cells and regulation of repair-related cytokines after bone marrow cell transplantation.2006

    • Author(s)
      Misao Y
    • Journal Title

      Cardiovascular Research. 69(2)

      Pages: 476-490

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hepatocyte growth factor gene therapy slows down the progression of diabetic nephropathy in db/db mice.2006

    • Author(s)
      Kagawa T.
    • Journal Title

      Nephron Physiology. 102(3-4)

      Pages: 92-102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification and isolation of embryonic stem cell-derived target cells by adenoviral conditional targeting.2006

    • Author(s)
      Takahashi T
    • Journal Title

      Molecular Therapy 14・5

      Pages: 673-683

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell cycle-specific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy : A promising implication of telomerase-dependent targeted cancer gene therapy.2006

    • Author(s)
      Murofushi Y
    • Journal Title

      International Journal of Oncology 29・3

      Pages: 681-688

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice : A comparative study to HGF.2006

    • Author(s)
      Khai NC
    • Journal Title

      Journal of Hepatology. 44・6

      Pages: 1046-1054

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating non-cardiomyocytes.2005

    • Author(s)
      Ushikoshi H
    • Journal Title

      Laboratory Investigation 85・7

      Pages: 862-873

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific and efficient viral replication.2005

    • Author(s)
      Kamizono J
    • Journal Title

      Cancer Research 65・12

      Pages: 5284-5291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An Efficient Construction of Conditionally Replicating Adenoviruses that Target Tumor Cells with Multiple Factors.2005

    • Author(s)
      Nagano S
    • Journal Title

      Gene Therapy 12・18

      Pages: 1385-1393

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adenoviral Gene Transduction of Hepatocyte Growth Factor Elicits Inhibitory Effects for Hepatoma.2005

    • Author(s)
      Yuge K
    • Journal Title

      International Journal Oncology 27・1

      Pages: 77-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diffuse Encephaloventriculitis and Substantial Leukoencephalopathy after Intraventricular Administration of Recombinant Adenovirus.2005

    • Author(s)
      Tada T
    • Journal Title

      Neurological Recearch 27・4

      Pages: 378-386

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Postinfarction gene therapy against transforming growth factor-beat signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure.2005

    • Author(s)
      Okada H
    • Journal Title

      Circulation 119・19

      Pages: 2430-2437

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ES細胞の心筋分化と再生医学への技術開発. ES細胞の分化.「幹細胞生物学の新たな展開」2005

    • Author(s)
      高橋 知之
    • Journal Title

      最新医学 60

      Pages: 28-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 多因子で増殖制御/癌特異標的化するアデノウイルスべクターのはじめての標準化作成技術.2005

    • Author(s)
      神囿 純一
    • Journal Title

      バイオテクノロジージャーナル 5・6

      Pages: 728-731

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating non-cardiomyocytes.2005

    • Author(s)
      Ushikoshi H
    • Journal Title

      Laboratory Investigation. 85(7)

      Pages: 862-873

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific and efficient viral replication.2005

    • Author(s)
      Kamizono J
    • Journal Title

      Cancer Research. 65(12)

      Pages: 5284-5291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An Efficient Construction of Conditionally Replicating Adenoviruses that Target Tumor Cells with Multiple Factors.2005

    • Author(s)
      Nagano S
    • Journal Title

      Gene Therapy. 12(18)

      Pages: 1385-1393

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adenoviral Gene Transduction of Hepatocyte Growth Factor Elicits Inhibitory Effects for Hepatoma.2005

    • Author(s)
      Yuge K
    • Journal Title

      International Journal of Oncology. 27(1)

      Pages: 77-85

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diffuse Encephaloventriculitis and Substantial Leukoencephalopathy after Intraventricular Administration of Recombinant Adenovirus.2005

    • Author(s)
      Tada T
    • Journal Title

      Neurological Research. 27(4)

      Pages: 378-386

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Postinfarction gene therapy against transforming growth factor-beat signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure.2005

    • Author(s)
      Okada H
    • Journal Title

      Circulation. 119(19)

      Pages: 2430-2437

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 7.HGF 急性/劇症肝炎.「細胞増殖因子と再生医療」(199-204)2006

    • Author(s)
      高橋 知之
    • Total Pages
      401
    • 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] 全日本鍼灸学会雑誌56 (1) : 16-262006

    • Author(s)
      小戝健一郎
    • Total Pages
      103
    • Publisher
      遺伝子治療と再生医学
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 再生医療(日本再生医療学会雑誌)5(1) : 43-512006

    • Author(s)
      高橋 知之
    • Total Pages
      155
    • Publisher
      ES細胞再生医学の新技術開発- ヒトES細胞と遺伝子治療技術-
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 細胞工学25(1) : 60-662006

    • Author(s)
      室伏 善照
    • Total Pages
      116
    • Publisher
      新世代癌遺伝子治療のための多因子で増殖制御/癌特異化するアデノウイルスの作製法
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 7.HGF 急性/劇症肝炎.「細胞増殖因子と再生医療」(199-204)2006

    • Author(s)
      高橋知之
    • Total Pages
      401
    • Publisher
      メディカルレビュー社
    • Related Report
      2006 Annual Research Report
  • [Book] 遺伝子治療と再生医学.全日本鍼灸学会雑誌 56巻1号,16-262006

    • Author(s)
      小戝健一郎
    • Total Pages
      103
    • Publisher
      社団法人 全日本鍼灸学会
    • Related Report
      2006 Annual Research Report
  • [Book] ES細胞再生医学の新技術開発- ヒトES細胞と遺伝子治療技術- 再生医療 5巻1号,43-512006

    • Author(s)
      高橋知之
    • Total Pages
      155
    • Publisher
      メディカルレビュー社
    • Related Report
      2006 Annual Research Report
  • [Book] 新世代癌遺伝子治療のための多因子で増殖制御/癌特異化するアデノウイルスの作製法.細胞工学 25巻1号,60-662006

    • Author(s)
      室伏善照
    • Total Pages
      116
    • Publisher
      秀潤社
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] ヘパリン結合性上皮増殖因子様増殖因子の新規医薬用途

    • Inventor(s)
      小戝健一郎, ニンチンカイ, 高橋知之
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2005-283085
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] Rett症候群を治療する医薬

    • Inventor(s)
      小戝健一郎, 飯盛健生, 松石豊次郎
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2004-328158
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] サービビン(Survivin)プロモーターを含む増殖型ベクターを有効成分とする医薬

    • Inventor(s)
      小戝健一郎, 神園純一, 永野聡
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2004-154431
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-23  

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