Self-organizing human cardiac microchambers mediated by geometric confinement
Open accessAbstract
Tissue morphogenesis and organ formation are the consequences of biochemical and biophysical cues that lead to cellular spatial patterning in development. To model such events in vitro, we use PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promotes spatial patterning via geometric confinement of the cell condensation process during epithelial-mesenchymal transition, forcing cells at the perimeter to express an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induce self-organizing lineage specification and creation of a beating human cardiac microchamber confined by the pattern geometry. These highly defined human cardiac microchambers can be used to study aspects of embryonic spatial patterning, early cardiac development and drug-induced developmental toxicity.
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Tissue engineering approaches for heart-on-a-chip or heart organoid models allow high control of the end construct but tend to be expensive, work-intensive, and not readily scalable.
“While these approaches allow for high control of the end construct, they tend to be expensive, work-intensive, and not readily scalable.”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [15]
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References 37 · Cited by 214
Research works printed but not linked: 1
- Huebsch N.. Automated video-based analysis of contractility and calcium flux in human-induced pluripotent stem cell-derived cardiomyocytes cultured over different spatial scales. Tissue Eng. C 21, 467– 479 (2015). PMC4410286 25333967
- Authors
- Ma, Z., Wang, J., Loskill, P., Huebsch, N., Koo, S., Svedlund, F. L., Marks, N. C., Hua, E. W., Grigoropoulos, C. P., Conklin, B. R., & Healy, K. E.
- Affiliations
- QB3 (US)
- University of California, Berkeley (US)
- Gladstone Institutes (US)
- Corresponding author
- Conklin, Bruce R.
- Healy, Kevin E.
- ORCID
- Venue
- Nature Communications
- Published
- 2015-07-14
- Volume
- 6
- Issue
- 1
- Pages
- 7413-7413
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4503387
- OpenAlex
- W2261586944
- Cited by
- 214
- References
- 37
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 23 · 2023: 23 · 2022: 22 · 2021: 30 · 2020: 24 · 2019: 11 · 2018: 22 · 2017: 14 · 2016: 11 · 2015: 5
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of Washington (EB-002027)
- National Institutes of Health (002027, NIH T32, UH3TR000487, UH2TR000487, EB-002027)
- National Heart, Lung, and Blood Institute (R01HL096525, U01HL100406, P01HL089707, U01HL098179, T32HL007544, R01HL108677)
- National Institute of Biomedical Imaging and Bioengineering (EB-002027, R21EB021003, P41EB002027)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- confined geometries, human pluripotent stem cells, Wnt/β-catenin signaling, epithelial-mesenchymal transition, cell condensation, Oct4, E-cadherin, lineage specification, beating cardiomyocytes, biophysical cues
- MeSH terms
- Cell Count, Cell Differentiation, Cell Movement, Cues, Heart, Humans, Models, Cardiovascular, Morphogenesis, Myocardium, Stress, Mechanical, Cadherins, Cell Lineage, Body Patterning, Myocytes, Cardiac, Cell Proliferation, Induced Pluripotent Stem Cells, Myofibroblasts, Epithelial-Mesenchymal Transition, Wnt Signaling Pathway, In Vitro Techniques
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