Biofabricating atherosclerotic plaques: In vitro engineering of a three-dimensional human fibroatheroma model

•No human in vitro model of late-stage atherosclerosis does exist.•Development of a 3D human cell-based spheroid model of late atherosclerotic lesion.•Comparison of the biofabricated model to plaques isolated from human carotids.•Intra-plaque population remodeling and viability effects of low-density lipoprotein.

Atherosclerotic plaques are cholesterol-induced inflammatory niches accumulating in the vascular sub-endothelial space. Cellular and extracellular composition of human plaques is maneuvered by local inflammation that leads to alterations in the original vascular microenvironment and to the recruitment of an invading fibrous layer (fibroatharoma). In the present study we introduce a bioengineered three-dimensional model of human fibroatheroma (ps-plaque) assembled with a tailored hanging-drop protocol. Using vi-SNE based multidimensional flow cytometry data analysis we compared the myeloid cell-populations in ps-plaques to those in plaques isolated from human carotid arteries. We observed that plasmacytoid and activated dendritic cells are the main myeloid components of human carotid plaques and that both cell types are present in the biofabricated model. We found that low-density lipoproteins affect cell viability and contribute to population polarization in ps-plaques. The current work describes the first human bioengineered in vitro model of late atherosclerotic lesion for the investigation of atherosclerosis aetiopathogenesis.

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