title: Growth factor therapy and autologous lymph node transfer in lymphedema.
abstract: BACKGROUND
  Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema.
  
  
  RESULTS
  The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node. Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (β-galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-C/D-treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved in the VEGF-C-treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the operated inguinal region postoperatively, whereas VEGF-C did not have this side effect.
  
  
  CONCLUSIONS
  These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the treatment of lymphedema.
authors.affiliation: Plastic Surgery, Turku University Central Hospital, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Lähteenvuo
authors.forename: Krista
authors.initials: K
authors.lastname: Honkonen
authors.forename: Tomi
authors.initials: T
authors.lastname: Tervala
authors.forename: Tuomas
authors.initials: T
authors.lastname: Tammela
authors.forename: Erkki
authors.initials: E
authors.lastname: Suominen
authors.forename: Johanna
authors.initials: J
authors.lastname: Lähteenvuo
authors.forename: Ivana
authors.initials: I
authors.lastname: Kholová
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Anne
authors.initials: A
authors.lastname: Saaristo
mesh_terms: D000260:Adenoviruses, Human; D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008198:Lymph Nodes / Q000637:transplantation*; D008209:Lymphedema / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D049291:Seroma / Q000628:therapy; D013552:Swine; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D001616:beta-Galactosidase