한빛사논문
한국과학기술연구원
Avelino Dos Santos Da Costa 1, Kopych Vadym 1,2, Kwideok Park 1,2
1Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
2Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Republic of Korea
Corresponding author: Kwideok Park
Abstract
Human health relies heavily on the vascular endothelium. Here, we propose a novel engineered endothelium model (EEM), which recapitulated both normal vascular function and pathology. An artificial basement membrane (aBM), where porous polyvinyl alcohol hydrogel was securely integrated with human fibroblast-derived, decellularized extracellular matrix on both sides was fabricated first and followed by endothelial cells (ECs) and pericytes (PCs) adhesion, respectively. Our EEM formed robust adherens junction (VE-cad) and built an impermeable barrier with time, along with the nitric oxide (NO) secretion. In our EEM, ECs and PCs interacted each other via aBM and led to hemoglobin alpha 1 (Hb-α1) development, which was involved in NO control and was strongly interconnected with VE-cad as well. A resilient property of EEM under inflammatory milieu was also confirmed by VE-cad and barrier recovery with time. In particular interest, foam cells formation, a hallmark of atherosclerotic initiation was successfully recapitulated in our EEM, where a series of sequential events were confirmed: human monocytes adhesion, transendothelial migration, and oxidized low-density lipoprotein uptake by macrophages. Collectively, our EEM is excellent in recapitulating not only normal endothelium but early pathologic one, thereby enabling EEM to be a physiologically relevant model for vascular study and disease modeling.
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