Anti-Atherogenic Effect of Stem Cell Nanovesicles Targeting Disturbed Flow Sites.
Jeong-Kee YoonDae-Hyun KimMi-Lan KangHyeon-Ki JangHyun-Ji ParkJung Bok LeeSe Won YiHye-Seon KimSewoom BaekDan Bi ParkJin YouSeong-Deok LeeYoshitaka SeiSong Ih AhnYoung Min ShinChang Soo KimSangsu BaeYongTae KimHak-Joon SungPublished in: Small (Weinheim an der Bergstrasse, Germany) (2020)
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.
Keyphrases
- endothelial cells
- anti inflammatory
- high glucose
- stem cells
- mesenchymal stem cells
- vascular endothelial growth factor
- high throughput
- cardiovascular disease
- pseudomonas aeruginosa
- single cell
- umbilical cord
- type diabetes
- circulating tumor
- pluripotent stem cells
- cell therapy
- induced pluripotent stem cells
- cancer therapy
- crispr cas
- single molecule
- low density lipoprotein
- drug delivery