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

淋巴水肿的治疗仍然有限，而且大部分无效。本研究的目的是探讨肝细胞生长因子（HGF）对淋巴水肿动物模型的治疗效果。免疫荧光分析淋巴内皮细胞（LEC）淋巴特异性标志物和HGF受体阳性。用人重组HGF处理LEC导致细胞生长和迁移的剂量依赖性增加。在大鼠尾部淋巴水肿模型中，通过破坏淋巴管每周转移HGF基因导致淋巴水肿厚度减少。此外，将HGF质粒DNA转移到腋窝淋巴结切除大鼠模型中。HGF组淋巴水肿体积明显减少。PDE系统的连续淋巴管造影显示hgf治疗动物的新淋巴管化渐进式扩展。这些数据表明，通过质粒转移表达HGF通过促进淋巴管生成来改善淋巴水肿。进一步的研究确定这种方法的临床应用将有利于淋巴水肿患者。

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.