Elucidation of Pathological Changs of Lymphedema

Research Project

Project/Area Number	25860583
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Cardiovascular medicine
Research Institution	The University of Tokyo
Principal Investigator	MOTOKI FUSA 東京大学, 医学部附属病院, 登録研究員 (70648253)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	リンパ浮腫 / リンパ管平滑筋細胞 / マウスモデル / リンパ管新生 / CD4陽性T細胞 / リンパ管硬化 / 炎症 / マクロファージ / リンパ球 / 免疫細胞 / VEGF-C
Outline of Final Research Achievements	Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed following cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using of human lymphatic vessels of lymphedema patients, I elucidated that the lymphatic tunica media and tunica intima consist mainly of phenotypical modulated smooth muscle cells (SMCs) and SMCs play pivotal roles in the development of lymphedema, as with the pathogenesis of various vascular disease. Furthermore, I made a mouse model of lymphedema and found that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. I found that CD4(+) T cells interact with macrophages to promote lymphangiogenesis.