Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema

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 gr...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 2011-02, Vol.123 (6), p.613-620
Hauptverfasser: LÄHTEENVUO, Markku, HONKONEN, Krista, TERVALA, Tomi, TAMMELA, Tuomas, SUOMINEN, Erkki, LÄHTEENVUO, Johanna, KHOLOVA, Ivana, ALITALO, Kari, YLÄ-HERTTUALA, Seppo, SAARISTO, Anne
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container_title Circulation (New York, N.Y.)
container_volume 123
creator LÄHTEENVUO, Markku
HONKONEN, Krista
TERVALA, Tomi
TAMMELA, Tuomas
SUOMINEN, Erkki
LÄHTEENVUO, Johanna
KHOLOVA, Ivana
ALITALO, Kari
YLÄ-HERTTUALA, Seppo
SAARISTO, Anne
description 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. 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. 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.
doi_str_mv 10.1161/circulationaha.110.965384
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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. 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. 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Miscellaneous</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Lymph Nodes - transplantation</subject><subject>Lymphedema - pathology</subject><subject>Lymphedema - surgery</subject><subject>Lymphedema - therapy</subject><subject>Medical sciences</subject><subject>Pharmacology. 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subjects Adenoviruses, Human
Animals
beta-Galactosidase - genetics
Biological and medical sciences
Blood and lymphatic vessels
Blood. Blood coagulation. Reticuloendothelial system
Cardiology. Vascular system
Disease Models, Animal
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Genetic Therapy - methods
Genetic Vectors
Lymph Nodes - transplantation
Lymphedema - pathology
Lymphedema - surgery
Lymphedema - therapy
Medical sciences
Pharmacology. Drug treatments
Seroma - therapy
Swine
Vascular Endothelial Growth Factor C - genetics
Vascular Endothelial Growth Factor D - genetics
title Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema
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