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Vascularized hiPSC-derived 3D cardiac microtissue on chip
Open accessAbstract
Functional vasculature is essential for delivering nutrients, oxygen, and cells to the heart and removing waste products. Here, we developed an in vitro vascularized human cardiac microtissue (MT) model based on human induced pluripotent stem cells (hiPSCs) in a microfluidic organ-on-chip by coculturing hiPSC-derived, pre-vascularized, cardiac MTs with vascular cells within a fibrin hydrogel. We showed that vascular networks spontaneously formed in and around these MTs and were lumenized and interconnected through anastomosis. Anastomosis was fluid flow dependent: continuous perfusion increased vessel density and thus enhanced the formation of the hybrid vessels. Vascularization further improved endothelial cell (EC)-cardiomyocyte communication via EC-derived paracrine factors, such as nitric oxide, and resulted in an enhanced inflammatory response. The platform sets the stage for studies on how organ-specific EC barriers respond to drugs or inflammatory stimuli.
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Perfusable blood vessels, although demonstrated in simpler cardiac constructs, have not yet been integrated into chamber systems.
“However, certain key features remain absent: perfusable blood vessels, although demonstrated in simpler cardiac constructs, have not yet been integrated into chamber systems (Arslan et al., 2023).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Arslan et al., 2023
The Discussion reports perfusable vessels in cardiac microtissues, supporting the claim about simpler cardiac constructs. Neither the Introduction nor the Discussion addresses whether perfusable vessels have been integrated into chamber systems, so the claim about their absence is unsupported by this source. (LLM, conf=0.84)
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A microfluidic platform integrating functional vascularized organoids-on-chip
Quintard, C., Tubbs, E., Jonsson, G., Jiao, J., Wang, J., Werschler, N., Laporte, C., Pitaval, A., Bah, T.-S., Pomeranz, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45710-4 · Cited by 387
Hecking, J., Cano-Jorge, M., Passier, R., & Rivera-Arbeláez, J. M. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1719533
Metadata
- Authors
- Arslan, U., Brescia, M., Meraviglia, V., Nahon, D. M., van Helden, R. W. J., Stein, J. M., van den Hil, F. E., van Meer, B. J., Vila Cuenca, M., Mummery, C. L., & Orlova, V. V.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Orlova, Valeria V.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2023-07
- Volume
- 18
- Issue
- 7
- Pages
- 1394-1404
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC10362508
- OpenAlex
- W4382723344
- Cited by
- 66
- References
- 1
- Citations by year
- 2026: 24 · 2025: 21 · 2024: 19 · 2023: 2
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Update notices
- erratum (2023-10-10)
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Funders
- Novo Nordisk Fonden (NNF21CC0073729)
- Horizon 2020 Framework Programme
- Horizon 2020 (812954)
- Ministerie van Onderwijs, Cultuur en Wetenschap (NWA-ORC 2019 1292.19.019)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (024.003.001)
- 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 cells, organ-on-a-chip, microfluidics, fibrin gel, vascular network formation, nitric oxide, paracrine signaling, inflammation, in vitro cardiac models
- MeSH terms
- Cell Differentiation, Humans, Neovascularization, Pathologic, Myocytes, Cardiac, Endothelial Cells, Induced Pluripotent Stem Cells
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