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Article

Biomimetic 3D Models for Investigating the Role of Monocytes and Macrophages in Atherosclerosis

1
Laboratory for Immuno Bioengineering Research and Applications, Division of Engineering, New York University Abu Dhabi, 129188 Abu Dhabi, UAE
2
Departament de Genètica i Microbiologia, Facultat de Biociències, Universitat Autònoma de Bellaterra, 08193 Barcelona, Spain
3
Department of Mechanical and Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY 11201, USA
*
Author to whom correspondence should be addressed.
Bioengineering 2020, 7(3), 113; https://doi.org/10.3390/bioengineering7030113
Received: 25 August 2020 / Revised: 12 September 2020 / Accepted: 14 September 2020 / Published: 16 September 2020
Atherosclerosis, the inflammation of artery walls due to the accumulation of lipids, is the most common underlying cause for cardiovascular diseases. Monocytes and macrophages are major cells that contribute to the initiation and progression of atherosclerotic plaques. During this process, an accumulation of LDL-laden macrophages (foam cells) and an alteration in the extracellular matrix (ECM) organization leads to a local vessel stiffening. Current in vitro models are carried out onto two-dimensional tissue culture plastic and cannot replicate the relevant microenvironments. To bridge the gap between in vitro and in vivo conditions, we utilized three-dimensional (3D) collagen matrices that allowed us to mimic the ECM stiffening during atherosclerosis by increasing collagen density. First, human monocytic THP-1 cells were embedded into 3D collagen matrices reconstituted at low and high density. Cells were subsequently differentiated into uncommitted macrophages (M0) and further activated into pro- (M1) and anti-inflammatory (M2) phenotypes. In order to mimic atherosclerotic conditions, cells were cultured in the presence of oxidized LDL (oxLDL) and analyzed in terms of oxLDL uptake capability and relevant receptors along with their cytokine secretomes. Although oxLDL uptake and larger lipid size could be observed in macrophages in a matrix dependent manner, monocytes showed higher numbers of oxLDL uptake cells. By analyzing major oxLDL uptake receptors, both monocytes and macrophages expressed lectin-like oxidized low-density lipoprotein receptor-1 (LOX1), while enhanced expression of scavenger receptor CD36 could be observed only in M2. Notably, by analyzing the secretome of macrophages exposed to oxLDL, we demonstrated that the cells could, in fact, secrete adipokines and growth factors in distinct patterns. Besides, oxLDL appeared to up-regulate MHCII expression in all cells, while an up-regulation of CD68, a pan-macrophage marker, was found only in monocytes, suggesting a possible differentiation of monocytes into a pro-inflammatory macrophage. Overall, our work demonstrated that collagen density in the plaque could be one of the major factors driving atherosclerotic progression via modulation of monocyte and macrophages behaviors. View Full-Text
Keywords: atherosclerosis; monocyte; macrophage; disease model; collagen; 3D cell culture; immunomechanobiology atherosclerosis; monocyte; macrophage; disease model; collagen; 3D cell culture; immunomechanobiology
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MDPI and ACS Style

Garcia-Sabaté, A.; Mohamed, W.K.E.; Sapudom, J.; Alatoom, A.; Al Safadi, L.; Teo, J.C.M. Biomimetic 3D Models for Investigating the Role of Monocytes and Macrophages in Atherosclerosis. Bioengineering 2020, 7, 113. https://doi.org/10.3390/bioengineering7030113

AMA Style

Garcia-Sabaté A, Mohamed WKE, Sapudom J, Alatoom A, Al Safadi L, Teo JCM. Biomimetic 3D Models for Investigating the Role of Monocytes and Macrophages in Atherosclerosis. Bioengineering. 2020; 7(3):113. https://doi.org/10.3390/bioengineering7030113

Chicago/Turabian Style

Garcia-Sabaté, Anna, Walaa K.E. Mohamed, Jiranuwat Sapudom, Aseel Alatoom, Layla Al Safadi, and Jeremy C.M. Teo 2020. "Biomimetic 3D Models for Investigating the Role of Monocytes and Macrophages in Atherosclerosis" Bioengineering 7, no. 3: 113. https://doi.org/10.3390/bioengineering7030113

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