A three-dimensional engineered artery model for in vitro atherosclerosis research

PLoS One. 2013 Nov 14;8(11):e79821. doi: 10.1371/journal.pone.0079821. eCollection 2013.

Abstract

The pathogenesis of atherosclerosis involves dysfunctions of vascular endothelial cells and smooth muscle cells as well as blood borne inflammatory cells such as monocyte-derived macrophages. In vitro experiments towards a better understanding of these dysfunctions are typically performed in two-dimensional cell culture systems. However, these models lack both the three-dimensional structure and the physiological pulsatile flow conditions of native arteries. We here describe the development and initial characterization of a tissue engineered artery equivalent, which is composed of human primary endothelial and smooth muscle cells and is exposed to flow in vitro. Histological analyses showed formation of a dense tissue composed of a tight monolayer of endothelial cells supported by a basement membrane and multiple smooth muscle cell layers. Both low (LDL) and high density lipoproteins (HDL) perfused through the artery equivalent were recovered both within endothelial cells and in the sub-endothelial intima. After activation of the endothelium with either tumour necrosis factor alpha (TNFα) or LDL, monocytes circulated through the model were found to adhere to the activated endothelium and to transmigrate into the intima. In conclusion, the described tissue engineered human artery equivalent model represents a significant step towards a relevant in vitro platform for the systematic assessment of pathogenic processes in atherosclerosis independently of any systemic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteries / anatomy & histology
  • Arteries / cytology
  • Arteries / drug effects
  • Arteries / physiology*
  • Biological Transport
  • Cell Movement / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology
  • Humans
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism
  • Lipoproteins, LDL / pharmacology
  • Models, Anatomic*
  • Monocytes / cytology
  • Monocytes / physiology
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Primary Cell Culture
  • Tissue Engineering*
  • Tissue Scaffolds
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tunica Intima / cytology
  • Tunica Intima / drug effects
  • Tunica Intima / physiology

Substances

  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Tumor Necrosis Factor-alpha

Grant support

This work was supported by grant from Zurich Integrative Human Physiology (ZIHP) to Arnold von Eckardstein, Simon Hoerstrup and Lucia Rohrer and by grants from the Swiss National Science Foundation to Simon Hoerstrup [310030-143992], Arnold von Eckardstein [31003A-130836/I.] and Benedikt Weber [320030-122273]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.