文献类型：期刊文献

英文题名：Platelet Membrane-Engineered Stem Cell-Derived Exosomes for Targeted Therapy Against Arterial Restenosis Via Promotion of Endothelial Repair and Inhibition of Neointima Hyperplasia

作者：Lu, Shan[1,2,3]; Wang, Ruihan[1,2,3]; Cai, Minghao[1,2,3]; Yuan, Chen[4]; Kan, Yuanqing[1,2,3]; Gao, Bin[1,2,3]; Zhang, Xu[7]; Xu, Yisheng[4]; Fua, Weiguo[1,2,3]; Yi, Si[1,2,3]; Guo, Daqiao[1,2,3]; Yu, Xiaohua[5,6]

机构：[1] Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, China; [2] Institute of Vascular Surgery, Fudan University, Shanghai, 200032, China; [3] National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China; [4] State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China; [5] Department of Orthopedics, The second Affliated Hospital of Zhejiang University School of Medicine, Zhejiang, Hangzhou, 310009, China; [6] Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Zhejiang, Hangzhou, 310009, China; [7] School of Public Health

年份：2024

外文期刊名：SSRN

收录：EI(收录号：20240269034)

语种：英文

外文关键词：Biomimetics - Cell culture - Cell membranes - Diseases - Endothelial cells - Hybrid systems - Macrophages - Platelets - Stem cells

摘要：Postinterventional restenosis, characterized by endothelial denudation, inflammatory cell infiltration, and neointima formation, is a major cause of treatment failure in those with peripheral artery diseases. Mesenchymal stem cell (MSC)–derived exosome therapy has shown potential to promote endothelial repair and inhibit neointima hyperplasia, but its therapeutic efficacy is hindered by insufficient targeting ability and limited tissue uptake. In this study, for restenosis rescue, we thus construct platelet-mimetic exosomes (PM-EXOs) using the membrane fusion method to mimic the platelet's inherent targeting towards arterial injuries and its evasion of the mononuclear phagocyte system. PM-EXOs promote cellular uptake by endothelial cells and macrophages, exerting proangiogenic and immunomodulatory effects via the delivery of functional microRNAs in vitro. In a mouse carotid artery wire-injury model, the intravenously injected PM-EXOs exhibit prolonged circulation and enhanced targeting of injured arteries compared to unmodified exosomes. Importantly, PM-EXOs successfully expedite re-endothelialization, ameliorate inflammatory response via repolarizing activated macrophages, and inhibit the formation of neointima without causing systemic toxicity. The targeting capacity and therapeutic effects of PM-EXOs are also validated in a rat carotid artery balloon-injury model. In summary, a biomimetic hybrid system of platelet membrane and MSC-derived exosome is constructed to ensure efficient targeting and realize the comprehensive treatment of arterial restenosis. ? 2024, The Authors. All rights reserved.