Marder, M. ; Remmert, C. ; Perschel, J.A. ; Otgonbayar, M. ; von Toerne, C. ; Hauck, S.M. ; Bushe, J. ; Feuchtinger, A. ; Sheikh, B. ; Moussus, M. ; Meier, M.
Stem cell-derived vessels-on-chip for cardiovascular disease modeling.
Cell Rep. 43:114008 (2024)
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.
Impact Factor
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 43,
Heft: 4,
Seiten: ,
Artikelnummer: 114008
Supplement: ,
Reihe
Verlag
Cell Press
Verlagsort
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Pioneer Campus (HPC)
CF Metabolomics & Proteomics (CF-MPC)
CF Pathology & Tissue Analytics (CF-PTA)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s)
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
30202 - Environmental Health
Forschungsfeld(er)
Pioneer Campus
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP-Element(e)
G-510002-001
G-505700-001
A-630600-001
G-555000-001
A-630700-001
Förderungen
ERC Consolidator Grant
EIslet project of the BMBF
Helmholtz Pioneer Campus
Copyright
Erfassungsdatum
2024-05-21