2009 Fiscal Year Final Research Report
Therapeutic Lymphangiogenesis for Lymphedema by Gene Therapy of Hepatocyte Growth Factor Plasmid DNA.
| Project/Area Number |
19390328
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
SASAJIMA Tadahiro Asahikawa Medical College, 医学部, 副学長 (20109515)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yukihiro 旭川医科大学, 医学部, 特任助教 (80540583)
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| Research Collaborator |
UCHIDA Hisashi 旭川医科大学, 医学部, 講師 (60301991)
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| Project Period (FY) |
2007 – 2009
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| Keywords | リンパ浮腫 / リンパ管新生 / 遺伝子治療 |
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| 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.
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