Abstract：
:Surgery or radiation therapy of metastatic cancer often damages lymph nodes, leading to secondary lymphedema. Here we show, using a newly established mouse model, that collecting lymphatic vessels can be regenerated and fused to lymph node transplants after lymph node removal. Treatment of lymph node-excised mice with adenovirally delivered vascular endothelial growth factor-C (VEGF-C) or VEGF-D induced robust growth of the lymphatic capillaries, which gradually underwent intrinsic remodeling, differentiation and maturation into functional collecting lymphatic vessels, including the formation of uniform endothelial cell-cell junctions and intraluminal valves. The vessels also reacquired pericyte contacts, which downregulated lymphatic capillary markers during vessel maturation. Growth factor therapy improved the outcome of lymph node transplantation, including functional reconstitution of the immunological barrier against tumor metastasis. These results show that growth factor-induced maturation of lymphatic vessels is possible in adult mice and provide a basis for future therapy of lymphedema.
journal_name
Nat Medjournal_title
Nature medicineauthors
Tammela T,Saaristo A,Holopainen T,Lyytikkä J,Kotronen A,Pitkonen M,Abo-Ramadan U,Ylä-Herttuala S,Petrova TV,Alitalo Kdoi
10.1038/nm1689subject
Has Abstractpub_date
2007-12-01 00:00:00pages
1458-66issue
12eissn
1078-8956issn
1546-170Xpii
nm1689journal_volume
13pub_type
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