4.8 Article

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

Journal

BIOMATERIALS
Volume 150, Issue -, Pages 49-59

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.09.034

Keywords

Bioengineering; Biofabrication; Disease modeling; Tissue engineering; vi-SNE; Atherosclerotic plaque

Funding

  1. 3R Foundation Switzerland [153-13]
  2. CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland
  3. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
  4. Institute of Regenerative Medicine of the University of Zurich

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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. (C) 2017 The Authors. Published by Elsevier Ltd.

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