Therapeutic Lymphangiogenesis for Lymphedema by Gene Therapy of Hepatocyte Growth Factor Plasmid DNA.

• Project/Area Number: 19390328
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Asahikawa Medical College
• Principal Investigator: SASAJIMA Tadahiro Asahikawa Medical College, 医学部, 副学長 (20109515)
• Co-Investigator(Kenkyū-buntansha): SAITO Yukihiro 旭川医科大学, 医学部, 特任助教 (80540583) ; 浅田 秀典 旭川医科大学, 医学部, 助教 (00292110) ; 内田 恒 旭川医科大学, 医学部, 助教 (60301991)
• Research Collaborator: UCHIDA Hisashi 旭川医科大学, 医学部, 講師 (60301991)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2009: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2008: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: リンパ浮腫 / リンパ管新生 / 遺伝子治療

Research Abstract

Treatment for lymphedema remains limited and largely ineffective. The goal of the present study was to investigate the therapeutic efficacy of hepatocyte growth factor (HGF) in animal models of lymphedema. Immunofluorescent analysis of lymphatic endothelial cell (LEC) was positive for lymphatic specific markers and the HGF receptor. The treatment of LEC with human recombinant HGF resulted in a dose-dependent increase in cell growth and migration. Weekly HGF gene transfer in a rat tail lymphedema model by disruption of lymphatic vessels resulted in a decrease in thickness of lymphedema. Furthermore, HGF plasmid DNA was transferred into an axillary lymph node-excised rat model. The volume of lymphedema was significantly decreased in the HGF group. Serial lymphangiography by PDE system revealed progressive extension of neo-lymphvascularization in HGF-treated animals. These data demonstrate that expression of HGF via plasmid transfer improves lymphedema via promotion of lymphangiogenesis. Further study to determine the clinical utility of this approach would be of benefit to patients with lymphedema.

Research Products

• [Journal Article] 肝細胞増殖因子によるリンパ浮腫遺伝子治療の基礎的検討. (2011)
  • Author(s): 齊藤幸裕、笹嶋唯博
  • Journal Title: リンパ学 (In press)
• [Journal Article] リンパ浮腫に対する遺伝子治療法の開発 (2011)
  • Author(s): 齊藤幸裕、笹嶋唯博, 他
  • Journal Title: 脈管学 (In press)
  • NAID: 130006262523
• [Presentation] Therapeutic Lymphangiogenesis for Lymphedema by Gene Therapy of Hepatocyte Growth Factor Plasmid DNA (2011)
  • Author(s): 齊藤幸裕、笹嶋唯博
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society ; OE-393
  • Place of Presentation: Yokohama, Japan
• [Presentation] 乳癌術後リンパ浮腫モデルへのHGFによるリンパ管新生遺伝子治療 (2010)
  • Author(s): 齊藤幸裕、笹嶋唯博
  • Organizer: 第110回日本外科学会定期学術集会;末梢血管-30P-265-4
  • Place of Presentation: 東京
• [Presentation] Therapeutic Lymphangiogenesis for Lymphedema by Gene Therapy of Hepatocyte Growth Factor Plasmid DNA (2010)
  • Author(s): 齊藤幸裕、笹嶋唯博
  • Organizer: 2010 International Union of Angiology
  • Place of Presentation: Buenos Aires, Argentina
• [Presentation] 肝細胞増殖因子によるリンパ浮腫遺伝子治療の基礎的検討 (2010)
  • Author(s): 齊藤幸裕、笹嶋唯博
  • Organizer: 第34回日本リンパ学会総会;シンポジウム1リンパ浮腫治療の新しい展開S1-1
  • Place of Presentation: 東京
• [Presentation] TRANSFECTION OF HUMAN HEPATOCYTE GROWTH FACTOR GENE AMELIORATES SECONDARY LYMPHEDEMA VIA LYMPHANGIOGENESIS (2010)
  • Author(s): 齊藤幸裕、笹嶋唯博, 他
  • Organizer: 16th JSGT Annual Meeting Oral Presentation-Genetic, Neuromuscular & Other Disease-II
  • Place of Presentation: Utsunomiya, Japan
• [Presentation] リンパ浮腫に対する遺伝子治療法の開発 (2010)
  • Author(s): 齊藤幸裕、笹嶋唯博, 他
  • Organizer: 第51回日本脈管学会総会;SY-4-6
  • Place of Presentation: 旭川
• [Presentation] Hepatocyte growth factor gene therapy for lymphedema. (2010)
  • Author(s): 齊藤幸裕、笹嶋唯博, 他
  • Organizer: 2nd Catholic VESSEL Update 2010
  • Place of Presentation: Seoul, Korea
• [Presentation] 乳癌術後リンパ浮腫モデルへのHGFによるリンパ管新生遺伝子治療 (2009)
  • Author(s): 齊藤幸裕
  • Organizer: 第50回日本脈管学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-29
• [Presentation] 乳癌術後リンパ浮腫モデルへのHGFによるリンパ管新生遺伝子治療 (2009)
  • Author(s): 齊藤幸裕、笹嶋唯博
  • Organizer: 第50回日本脈管学会総会;0-1-4
  • Place of Presentation: 東京
• [Presentation] リンパ浮腫に対するHGF遺伝子治療-臨床応用を目指した新たなステップ (2008)
  • Author(s): 齊藤幸裕
  • Organizer: 第49回日本脈管学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-24
• [Presentation] リンパ浮腫に対するHGF遺伝子治療-臨床応用を目指した新たなステップ (2008)
  • Author(s): 齊藤幸裕、中神啓徳、東信良、森下竜一、金田安史、笹嶋唯博
  • Organizer: 第49回日本脈管学会総会;0-15-1
  • Place of Presentation: 東京
• [Presentation] Hepatocyte growth factor ameliorates secondary lymphedema via promotion of lymphangiogenesis (2007)
  • Author(s): Yukihiro Saito
  • Organizer: 2007 Asian Chapter Congress of the Intemational Union of Angiology
  • Place of Presentation: 台北
  • Year and Date: 2007-09-05
• [Presentation] Hepatocyte growth factor ameliorates secondary lymphedema via promotion of lymphangiogenesis. (2007)
  • Author(s): 齊藤幸裕、笹嶋唯博, 他
  • Organizer: 2007 Asian Chapter Congress of the International Union of Angiology ; S15-04
  • Place of Presentation: Taipei, Taiwan
• [Remarks] ホームページ等
  • URL: http://www.asahikawa-med-surgery.net/jp/home/index.html
• [Patent(Industrial Property Rights)] リンパ管新生促進剤 (2008)
  • Inventor(s): 齊藤幸裕, 他3名
  • Industrial Property Rights Holder: アンジェスMG株式会社
  • Acquisition Date: 2008-04-18
• [Patent(Industrial Property Rights)] リンパ管新生促進剤 (2006)
  • Inventor(s): 齊藤幸裕, 他3名
  • Industrial Property Rights Holder: アンジェスMG株式会社
  • Filing Date: 2006-07-28
  • Overseas