Pro-vs anti-stenotic capacities of type-Ⅰ vs type-Ⅱ human induced pluripotent-derived endothelial cells

作     者：Miwako Nishio Masako Nakahara Koichi Saeki Katsuhito Fujiu Hiroshi Iwata Ichiro Manabe Akira Yuo Kumiko Saeki 

作者机构：Department of Disease Control Research Institute National Center for Global Health and Medicine Section of Cell Engineering Department of Basic Research DNAVEC Center ID Pharma Co. Ltd. Department of Cardiovascular Medicine Graduate School of Medicine the University of Tokyo Translational Systems Biology and Medicine Initiative the University of Tokyo PRESTO Japan Science and Technology Agency 

出 版 物：《World Journal of Translational Medicine》 (世界转化医学杂志)

年 卷 期：2015年第4卷第3期

页      面：113-122页

学科分类：10[医学] 

基　　金：Supported by Grant-in-Aid from the Ministry of Health Labour and Welfare of Japan(KHD1017) by that from JST PRESTO 

主　　题：Vascular endothelial cells Vasa vasorum Arteriostenosis Wire injury Human induced pluripotent stem cells 

摘      要：AIM:To verify in vivo relevance of the categorization of human vascular endothelial cells(VECs)into type-I(proproliferative)and type-II(anti-proliferative).METHODS:Endothelial layers of murine femoral arteries were removed by wire injury(WI)operation,a common technique to induce ***-I and type-II VECs produced from human induced pluripotent stem cells(iPSCs),whose characters were previously determined by their effects on the proliferation of vascular smooth muscle cells in in vitro co-culture experiments,were mixed with Matrigel?*** mixtures were injected into subcutaneous spaces around WI-operated femoral arteries for the transplanted human iPSC-derived VECs(iPSdECs)to take a route to the luminal surface via vasa vasorum,a nutrient microvessel for larger *** of the femoral arteries were examined over *** presence of human iPSdECs was checked by immunostaining studies using an antibody that specifically recognizes human *** of stenosis of the femoral arteries were calculated after three *** determine the optimal experimental condition,xenotransplantation experiments were performed under various conditions using immunocompromised mice as well as immunocompetent mice with or without administration of ***:Because immunocompromised mice showed unexpected resistance to WI-induced arteriostenosis,we performed xenotransplantation experiments using immunocompetent mice along with immunosuppressant *** one week,luminal surfaces of the WI-operated arteries were completely covered by human iPSdECs,showing the efficacy of our novel transplantation *** three weeks,type-IiPSdECs-transplanted arteries underwent total stenosis,while type-II-iPSdECs-transplanted arteries remained ***,untransplanted arteries of immunosuppressant-treated mice also remained intact by unknown *** found that transplanted human VECs had already been replaced by murine endothel