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Angiogenesis with bone marrow cells and gene therapy

Research Project

Project/Area Number 14370448
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOsaka Medical College

Principal Investigator

MIYATAKE Shin-ichi  Osaka Medical College, Faculty of medicine, Associate Professor, 医学部, 助教授 (90209916)

Co-Investigator(Kenkyū-buntansha) KUROIWA Toshihiko  Osaka Medical College, Faculty of medicine, Professor, 医学部, 教授 (30178115)
KAJIMOTO Yoshinaga  Osaka Medical College, Faculty of medicine, Associate Professor, 医学部, 講師 (30224413)
DEGUCHI Jun  Osaka Medical College, Faculty of medicine, Associate Professor, 医学部, 講師 (00288713)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2003: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥7,100,000 (Direct Cost: ¥7,100,000)
Keywordsbone marrow cell / cerebral infarction / FGF-2 / gene therapy / herpes simplex virus / neurogenesis / transplantation / vasculogenesis
Research Abstract

To develop the new therapeutic modality for occlusive cerebrovascular disease, we try to combine the cell therapy using bone marrow cells and gene therapy using viral vectors. We performed next 3 projects.
1)Direct gene therapy using FGF-2-expressing adenoviral vectors into lateral ventricle in MCA occlusiojn rat.
2)Development of new, replication incompetent herpes simplex virus (HSV) vector expressing FGF-2, VEGF and HGF. Also new attempt to transfer the above gene into bone marrow cells using this new vectors.
3)Therapeutic experiment using mesenchymal stromal cells (MSC) and this new developed HSV vectors.
Results :
1)Direct gene delivery of FGF-2 decreased the infarction size and improved the neurological symptom after MCA occlusion.
2)Newly constructed HSV showed marked gene transduction efficacy into mesenchymal stromal cells and exhibited stable and strong gene expression in the MSC. No viral replication in MSC was recognized.
3)Intralesional transplantation of MSC improved the neurological symptom in MCA occlusion rat, while, that of MSC transduced HGF gene by HSV vector exhibited more improvement of the symptom in model rat.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Norihiro Matsuoka, Shin-Ichi Miyatake, et al.: "Adenovirus-mediated Gene Transfer of FGF-2 Promotes Neurogenesis after Forbrain Ischemia in Gerbils"Stroke. 34. 1519-1525 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinji Kaihara, Shin-Ichi Miyatake, et al.: "Overexpression of bone morphogenetic protein-3b (BMP-3b) using an adenoviral vector promote the osteoblastic differentiation in C2C12 Cells and augment the bone formation induced by bone morphogenetic protein-2 (BMP-2) in rats induced by bone morphogentic protein-2 (BMP-2) in rats"Life Science. 72. 1683-1693 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroyasu Yamashiro, shin-Ichi Miyatake, et al.: "Spontaneous Proliferation and Adipogenesis of Human Adipose Tissue-derived Vascular-stromal Cells Infected with Basic Fibroblast Growth Factor Gene"Tissue Engineering. 9. 881-892 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshitaka Yamada, Shin-Ichi Miyatake, et al.: "Transcriptional expression of survivin and survivin splice variants in human brain tumors"J Neurosurgery. 99. 881-892 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ninomiya M, Miyatake S, et al.: "Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model"Gene Therapy. 10. 1152-1160 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishi S, Miyatake S, et al.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia"J Vasc Surg. 33. 629-638 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takuji Watanabe, Shin-Ichi Miyatake, et al.: "Post-ischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats"J Cerebral Blood Flow and Metabol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Norihiro Matsuoka, Kazuhiro Ishii, Masayuki Akimoto, Hirofumi Hamada, Nobuo Hashimoto, Shin-Ichi Miyatake: "Overexpression of bFGF and Bcl-xL with adenoviral vectors protects primarily cultured-neurons against glutamate insult.cultured-neurons against glutamate insult."Neurosurgery. 50(4). 857-863 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shin-Ichi Miyatake: "Gene Therapy Using Tissue-Specific Replication Competent HSV"Human Cell. 15. 130-137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Norihiro Matsuoka, Kazuhiko Nozaki, Yasushi Takagi, Masaki Nishimura, Shin-Ichi Miyatake, Nobuo Hashimoto: "Adenovirus-mediated Gene Transfer"Stroke. 34(6). 1519-1525 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinji Kaihara, Kazuhisa Bessho, Yasunori Okubo, Junya Sonobe, Yasato Komatsu, Masako Miura, Shin-Ichi Miyatake, Kazuwa Nakao, Tadahiko Iizuka: "Overexpression of bone morphogentic protein-3b (BMP-3b) using an adenoviral vector promote the ostoblastic differentiation in C2C12 cells and augment the bone formation induced by bone morphogentic protein-2 (BMP-2) in rats."Life Science. 72. 1683-1693 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroyasu Yamashiro^1, Takashi Inamoto^<1, 2>, Hironori Kato^1, Michio Yagi^1, Megumi Takeuchi^1, Shin-Ichi Miyatake, Yasuhiko Tabata^3, Yoshio Yamaoka^1: "Spontaneous Proliferation and Adipogenesis of Human Adipose Tissue-derived Vascular-stromal Cells Infected with Basic Fibroblast Growth Factor Gene."Tissue Engineering. 9(5). 881-892 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshitaka Yamada, Toshihiko Kuroiwa, Toshimasa Nakagawa, Yoshinaga Kajimoto, Takehiko Dohi, Haruhito Azuma, Motomu Tsuji, Kazuhiro Kami, Shin-Ichi Miyatake: "Transcriptional expression of survivin and survivin splice variants in human brain tumors."J Neurosurgery. 99. 738-745 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ninomiya M, Koyama H, Miyata T, Hamada H, Miyatake S, Shigematsu H, Takamoto S.: "Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model."Gene Ther.. 10(14). 1152-1160 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii S, Koyama H, Miyata T, Nishikage S, Hamada H, Miyatake S, Shigematsu H.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia."J Vasc Surg.. 39(3). 629-638 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Norihiro Matsuoka, Shin-Ichi Miyatake et al.: "Adenovirus-mediated Gene Transfer of FGF-2 Promotes Neurogenesis after Forebrain Ischemia in Gerbils"Stroke. 34. 1519-1525 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinji Kaihara, Shin-Ichi Miyatake, et al.: "Overexpression of bone morphogentic protein-3b (BMP-3b) using an adenoviral vector promote the ostoblastic differentiation in C2C12 cells and augment the bone formation induced by bone morphogentic protein-2 (BMP-2) in ratsinduced by bone morphogentic protein-2 (BMP-2) in rats"Life Science. 72. 1683-1693 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroyasu Yamashiro, Shin-Ichi Miyatake, et al.: "Spontaneous Proliferation and Adipogenesis of Human Adipose Tissue-derived Vascular-stromal Cells Infected with Basic Fibroblast Growth Factor Gene"Tissue Engineering. 9. 881-892 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshitaka Yamada, Shin-Ichi Miyatake, et al.: "Transcriptional expression of survivin and survivin splice variants in human brain tumors"J Neurosurgery. 99. 881-892 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ninomiya M, Miyatake S, et al.: "Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model"Gene Therapy. 10. 1152-1160 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishi S, Miyatake S, et al.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia"J Vasc Surg. 33. 629-638 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takuji Watanabe, Shin-Ichi Miyatake, et al.: "Post-ischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurological outcome and reduces infarct volume after transient focal cerebral ischemia in rats"Cerebral Blood Flow and Metabol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 宮武伸一: "複製可能型単純ヘルペスウイルスを用いた遺伝子治療"外科. 64. 281-287 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Norihiro Matsuoke, Shin-Ichi Miyatake, et al.: "Overexpression of bFGF and Bcl-xL with adenoviral vectors protects primarily cultured-neurons against glutamate insult"Neurosurgery. 50. 857-862 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shin-Ichi Miyatake: "Gene Therapy Using Tissue-Specific Replication Competent HSV Human Cell"Human Cell. 15. 130-137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Norihiro Matsuoka, Shin-Ichi Miyatake, et al.: "Adenovirus-mediated Gene Transfer of FGF-2 Promotes Neurogenesis after Forebrain Ischemia in Gerbils"Stroke in press.

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinji Kaihara, Shin-Ichi Miyatake, et al.: "Overexpression of bone morphogentic protein-3b(BMP-3b) using an adenoviral vector promote the ostoblastic differentiation in C2C12 cells and augment the bone formation induced by bone morphogentic protein-2(BMP-2) in rats"Life Science. 72. 1683-1693 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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