Utilization of an Artery-on-a-Chip to Unravel Novel Regulators and Therapeutic Targets in Vascular Diseases

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Valentina Paloschi - , Technical University of Munich (Author)
  • Jessica Pauli - , Technical University of Munich (Author)
  • Greg Winski - , Karolinska Institutet (Author)
  • Zhiyuan Wu - , Technical University of Munich (Author)
  • Zhaolong Li - , Technical University of Munich (Author)
  • Lorenzo Botti - , University of Bergamo (Author)
  • Sandro Meucci - , Micronit Microtechnologies (Author)
  • Pierangelo Conti - , University of Bergamo (Author)
  • Felix Rogowitz - , FLUIGENT Deutschland GmbH (Author)
  • Nadiya Glukha - , Technical University of Munich (Author)
  • Nora Hummel - , Technical University of Munich (Author)
  • Albert Busch - , Department of Visceral, Thoracic and Vascular Surgery (Author)
  • Ekaterina Chernogubova - , Karolinska Institutet (Author)
  • Hong Jin - , Karolinska Institutet (Author)
  • Nadja Sachs - , Technical University of Munich (Author)
  • Hans-Henning Eckstein - , Technical University of Munich (Author)
  • Anne Dueck - , Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Author)
  • Reinier A Boon - , Amsterdam University Medical Centers (UMC) (Author)
  • Andreas R Bausch - , Technical University of Munich (Author)
  • Lars Maegdefessel - , Technical University of Munich (Author)

Abstract

In this study, organ-on-chip technology is used to develop an in vitro model of medium-to-large size arteries, the artery-on-a-chip (AoC), with the objective to recapitulate the structure of the arterial wall and the relevant hemodynamic forces affecting luminal cells. AoCs exposed either to in vivo-like shear stress values or kept in static conditions are assessed to generate a panel of novel genes modulated by shear stress. Considering the crucial role played by shear stress alterations in carotid arteries affected by atherosclerosis (CAD) and abdominal aortic aneurysms (AAA) disease development/progression, a patient cohort of hemodynamically relevant specimens is utilized, consisting of diseased and non-diseased (internal control) vessel regions from the same patient. Genes activated by shear stress follow the same expression pattern in non-diseased segments of human vessels. Single cell RNA sequencing (scRNA-seq) enables to discriminate the unique cell subpopulations between non-diseased and diseased vessel portions, revealing an enrichment of flow activated genes in structural cells originating from non-diseased specimens. Furthermore, the AoC served as a platform for drug-testing. It reproduced the effects of a therapeutic agent (lenvatinib) previously used in preclinical AAA studies, therefore extending the understanding of its therapeutic effect through a multicellular structure.

Details

Original languageEnglish
Article number2302907
Pages (from-to)e2302907
JournalAdvanced healthcare materials
Volume13
Issue number6
Publication statusE-pub ahead of print - 5 Oct 2023
Peer-reviewedYes

External IDs

Scopus 85174406928

Keywords

Sustainable Development Goals