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J Surg Res. 2015 Jun 1;196(1):200-7. doi: 10.1016/j.jss.2015.02.031. Epub 2015 Feb 19.

Growth factor therapy and lymph node graft for lymphedema.

Author information

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.

KEYWORDS:

Lymph node transfer; Lymphedema; Vascular endothelial growth factor

PMID:
25777822
DOI:
10.1016/j.jss.2015.02.031
[Indexed for MEDLINE]

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