Human heart-on-a-chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC-derived cardiomyocytes
Open accessAbstract
In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell-cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted integrity among vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The tri-culture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the bi-culture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such tri-culture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior.
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Coculture may improve hCM survival and limited proliferation, increasing the number of functional cardiomyocytes.
“In addition, coculture may improve hCM survival and limited proliferation, increasing the number of functional cardiomyocytes.[ 57 , 58 , 59 ]”
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 [58]
The Results section reports greater contractility and a higher percentage of cells expressing cardiomyocyte markers in the tri-culture group, supporting improved cardiac function under coculture. It does not show that coculture improved cardiomyocyte survival or proliferation, or establish an increase in their absolute number; searches for survival and proliferation found no such results in our copy. Page numbers were not provided. (LLM, conf=0.84)
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- Authors
- Liu, Y., Kamran, R., Han, X., Wang, M., Li, Q., Lai, D., Naruse, K., & Takahashi, K.
- Affiliations
- Okayama University (JP)
- Corresponding author
- Takahashi, Ken
- Venue
- Scientific Reports
- Published
- 2024-08-08
- Volume
- 14
- Issue
- 1
- Pages
- 18063-18063
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC11310341
- OpenAlex
- W4401426824
- Cited by
- 47
- References
- 60
- Citations by year
- 2026: 27 · 2025: 19 · 2024: 1
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Okayama University Scientific Achievement Repository (Okayama University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Society for the Promotion of Science (21H04960, 20H04518)
- 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
- heart-on-a-chip, organ-on-a-chip, iPSC-derived cardiomyocytes, fibroblasts, vascular endothelial cells, microfluidics, endothelial cell alignment, shear flow, endothelial permeability, cardiomyocyte contractility, IRX4, noradrenaline response, cardiac tissue engineering
- MeSH terms
- Microphysiological Systems, Cell Differentiation, Cells, Cultured, Fibroblasts, Humans, Coculture Techniques, Myocytes, Cardiac, Endothelial Cells, Lab-On-A-Chip Devices, Induced Pluripotent Stem Cells
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