Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation
Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation
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DOI：
10.1038/nm1689
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发表时间：
2007-12-01
期刊：
影响因子：
82.9
通讯作者：
Alitalo, Kari
中科院分区：
文献类型：
--
作者：
Tammela, Tuomas;Saaristo, Anne;Alitalo, Kari
转移性癌症的手术或放射治疗通常会损伤淋巴结，导致继发性水肿。在这里，我们表明，使用一个新建立的小鼠模型，收集淋巴管可以再生和融合淋巴结切除后的淋巴结移植。用腺病毒递送的血管内皮生长因子-C（VEGF-C）或VEGF-D治疗淋巴结切除的小鼠诱导毛细淋巴管的稳健生长，毛细淋巴管逐渐经历内在重塑、分化和成熟为功能性集合淋巴管，包括形成均匀的内皮细胞-细胞连接和管腔内瓣膜。血管还重新获得周细胞接触，这在血管成熟过程中下调毛细淋巴管标记物。生长因子治疗可改善淋巴结移植的预后，包括重建抗肿瘤转移的免疫屏障。这些结果表明，生长因子诱导成熟的淋巴管在成年小鼠是可能的，并提供了未来的治疗水肿的基础。
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.