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Marder, M. ; Remmert, C. ; Perschel, J.A. ; Otgonbayar, M. ; von Toerne, C. ; Hauck, S.M. ; Bushe, J. ; Feuchtinger, A. ; Sheikh, B.N. ; Moussus, M. ; Meier, M.

Stem cell-derived vessels-on-chip for cardiovascular disease modeling.

Cell Rep. 43:114008 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The metabolic syndrome is accompanied by vascular complications. Human in vitro disease models are hence required to better understand vascular dysfunctions and guide clinical therapies. Here, we engineered an open microfluidic vessel-on-chip platform that integrates human pluripotent stem cell-derived endothelial cells (SC-ECs). The open microfluidic design enables seamless integration with state-of-the-art analytical technologies, including single-cell RNA sequencing, proteomics by mass spectrometry, and high-resolution imaging. Beyond previous systems, we report SC-EC maturation by means of barrier formation, arterial toning, and high nitric oxide synthesis levels under gravity-driven flow. Functionally, we corroborate the hallmarks of early-onset atherosclerosis with low sample volumes and cell numbers under flow conditions by determining proteome and secretome changes in SC-ECs stimulated with oxidized low-density lipoprotein and free fatty acids. More broadly, our organ-on-chip platform enables the modeling of patient-specific human endothelial tissue and has the potential to become a general tool for animal-free vascular research.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cp: Stem Cell Research ; Atherosclerosis ; Disease Modeling ; Hipsc-derived Endothelial Cells ; Open Microfluidics ; Single-cell Sequencing ; Vessel-on-chip; Nitric-oxide Synthase; Shear-stress; Enrichment Analysis; Endothelial-cells; Web Server; Vitronectin; Expression; Generation; Platform
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 43, Issue: 4, Pages: , Article Number: 114008 Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Core Facility Metabolomics and Proteomics (CF-MPC)
Core Facilty Pathology and Tissue Analytics (CF-PTA)
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG)
Grants ERC Consolidator Grant
EIslet project of the BMBF
Helmholtz Pioneer Campus