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Cited by 423D Printing in Biomedical ResearchTissue Engineering and Regenerative MedicinePluripotent Stem Cells Research

Functional microvascularization of human myocardium in vitro

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King, Oisín, Cruz-Moreira, Daniela, Sayed, Alaa, Kermani, Fatemeh, Kit-Anan, Worrapong, Sunyovszki, Ilona, Wang, Brian X., Downing, Barrett +6 more·2022·Cell Reports Methods
DOI 10.1016/j.crmeth.2022.100280PMC PMC9499876
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Abstract

In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research.

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  • hCMEC supports efficient metabolic and electrical function by increasing oxygenation and electrophysiological properties through the release of vascular endothelial growth factor (VEGF) and nitric oxide.

    “Moreover hCMEC supports efficient metabolic and electrical function by increasing oxygenation and electrophysiological properties through the release of vascular endothelial growth factor (VEGF) and nitric oxide.[ 55 , 56 ]”

    From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [56]

    The Results section reports that human cardiac microvascular endothelial cell co-culture altered iPSC-cardiomyocyte electrophysiology, including membrane potentials and arrhythmia measures. It does not establish improved oxygenation or metabolic function, or show that VEGF and nitric oxide released by those cells caused the effects. In STAR★Methods, VEGF is described as a supplement added to the culture, not as a measured endothelial-cell release (page numbers unavailable). (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
King, O., Cruz-Moreira, D., Sayed, A., Kermani, F., Kit-Anan, W., Sunyovszki, I., Wang, B. X., Downing, B., Fourre, J., Hachim, D., Randi, A. M., Stevens, M. M., Rasponi, M., & Terracciano, C. M.
Affiliations
  • Imperial College London (GB)
  • Politecnico di Milano (IT)
Corresponding author
  • King, Oisín
  • Terracciano, Cesare M.
ORCID
Venue
Cell Reports Methods
Publisher
Elsevier BV
Published
2022-09
Volume
2
Issue
9
Pages
100280
ISSN
2667-2375 (ISSN-L)
DOI
10.1016/j.crmeth.2022.100280
PMC
PMC9499876
OpenAlex
W4293462382
Cited by
42
References
8
Citations by year
2026: 9 · 2025: 11 · 2024: 10 · 2023: 12
FWCI
2.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports Methods (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Virtual Community of Pathological Anatomy (University of Castilla La Mancha) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • British Heart Foundation (FS/16/56/32732, NP001-06-2015, MED_CT_17_079)
  • Universität Heidelberg
  • Gladstone Institutes
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
human induced pluripotent stem cell-derived cardiomyocytes, cardiac microvascular endothelial cells, co-culture, heart-on-a-chip, microfluidic perfusion, beating frequency, action potential, calcium handling, pulsatile flow, red blood cell imaging, 3D co-culture
MeSH terms
Humans, Myocardium, Coculture Techniques, Myocytes, Cardiac, Endothelial Cells, Induced Pluripotent Stem Cells

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