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Anti‐Atherogenic Effect of Stem Cell Nanovesicles Targeting Disturbed Flow Sites
Authors:Jeong‐Kee Yoon  Dae‐Hyun Kim  Mi‐Lan Kang  Hyeon‐Ki Jang  Hyun‐Ji Park  Jung Bok Lee  Se Won Yi  Hye‐Seon Kim  Sewoom Baek  Dan Bi Park  Jin You  Seong‐Deok Lee  Yoshitaka Sei  Song Ih Ahn  Young Min Shin  Chang Soo Kim  Sangsu Bae  YongTae Kim  Hak‐Joon Sung
Abstract:Atherosclerosis development leads to irreversible cascades, highlighting the unmet need for improved methods of early diagnosis and prevention. Disturbed flow formation is one of the earliest atherogenic events, resulting in increased endothelial permeability and subsequent monocyte recruitment. Here, a mesenchymal stem cell (MSC)‐derived nanovesicle (NV) that can target disturbed flow sites with the peptide GSPREYTSYMPH (PREY) (PMSC‐NVs) is presented which is selected through phage display screening of a hundred million peptides. The PMSC‐NVs are effectively produced from human MSCs (hMSCs) using plasmid DNA designed to functionalize the cell membrane with PREY. The potent anti‐inflammatory and pro‐endothelial recovery effects are confirmed, similar to those of hMSCs, employing mouse and porcine partial carotid artery ligation models as well as a microfluidic disturbed flow model with human carotid artery‐derived endothelial cells. This nanoscale platform is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.
Keywords:atherosclerosis  disturbed blood flow  mesenchymal stem cells  nanovesicles  plasmid design
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