Tomi V Tervala1, Pauliina Hartiala2, Tuomas Tammela3, Mikko T Visuri2, Seppo Ylä-Herttuala4, Kari Alitalo3, Anne M Saarikko5. 1. Department of Plastic Surgery, Kuopio University Hospital, Kuopio, Finland. Electronic address: tomi.tervala@kuh.fi. 2. Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland. 3. Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland. 4. Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland. 5. Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland; Department of Plastic Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Abstract
BACKGROUND: Lymphedema still remains an unsolved problem. Secondary lymphedema often develops after cancer operations or radiation therapy, especially in breast cancer patients. Using a mouse model, we show here that the lymphatic network can be regenerated using lymphatic vascular growth factor therapy in combination with lymph node transfer. MATERIALS AND METHODS: We have compared the therapeutic effects of different vascular endothelial growth factors (VEGF-C, VEGF-D, VEGF-C156S, and VEGF-A), in combination with lymph node transfer in mouse axilla. The lymphangiogenic effects of the growth factor therapy were examined at 3 mo postoperatively. RESULTS: VEGF therapy with VEGF-C and VEGF-D induced growth of new lymphatic vessels in the defect area, and VEGF-C also improved lymphatic vessel function compared with that of controls. VEGF-C156S induced moderate lymphangiogenesis, but the effect remained statistically nonsignificant. Prolymphangiogenic growth factors (VEGF-C, -D, and -C156S) also improved lymph node survival as compared with those of the VEGF-A and control group. VEGF-C, which activates both vascular endothelial growth factor receptor 2 and vascular endothelial growth factor receptor 3, gave the best therapeutic effect in this experimental lymphedema model. CONCLUSIONS: These results support our goal to treat secondary lymphedema by combining lymph node transfer with the growth factor therapy. VEGF-C provides the preferred alternative for growth factor therapy of lymphedema when compared with other VEGF-family growth factors, due to the superior lymphangiogenic response and minor blood vascular effects.
BACKGROUND:Lymphedema still remains an unsolved problem. Secondary lymphedema often develops after cancer operations or radiation therapy, especially in breast cancerpatients. Using a mouse model, we show here that the lymphatic network can be regenerated using lymphatic vascular growth factor therapy in combination with lymph node transfer. MATERIALS AND METHODS: We have compared the therapeutic effects of different vascular endothelial growth factors (VEGF-C, VEGF-D, VEGF-C156S, and VEGF-A), in combination with lymph node transfer in mouse axilla. The lymphangiogenic effects of the growth factor therapy were examined at 3 mo postoperatively. RESULTS:VEGF therapy with VEGF-C and VEGF-D induced growth of new lymphatic vessels in the defect area, and VEGF-C also improved lymphatic vessel function compared with that of controls. VEGF-C156S induced moderate lymphangiogenesis, but the effect remained statistically nonsignificant. Prolymphangiogenic growth factors (VEGF-C, -D, and -C156S) also improved lymph node survival as compared with those of the VEGF-A and control group. VEGF-C, which activates both vascular endothelial growth factor receptor 2 and vascular endothelial growth factor receptor 3, gave the best therapeutic effect in this experimental lymphedema model. CONCLUSIONS: These results support our goal to treat secondary lymphedema by combining lymph node transfer with the growth factor therapy. VEGF-C provides the preferred alternative for growth factor therapy of lymphedema when compared with other VEGF-family growth factors, due to the superior lymphangiogenic response and minor blood vascular effects.
Authors: Echoe M Bouta; Richard D Bell; Homaira Rahimi; Lianping Xing; Ronald W Wood; Clifton O Bingham; Christopher T Ritchlin; Edward M Schwarz Journal: Nat Rev Rheumatol Date: 2018-01-11 Impact factor: 20.543
Authors: Natalia Davydova; Nicole C Harris; Sally Roufail; Sophie Paquet-Fifield; Musarat Ishaq; Victor A Streltsov; Steven P Williams; Tara Karnezis; Steven A Stacker; Marc G Achen Journal: J Biol Chem Date: 2016-11-16 Impact factor: 5.157