Cited by 214Pluripotent Stem Cells ResearchCellular Mechanics and InteractionsTissue Engineering and Regenerative Medicine

Self-organizing human cardiac microchambers mediated by geometric confinement

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Ma, Zhen, Wang, Jason, Loskill, Peter, Huebsch, Nathaniel, Koo, Sangmo, Svedlund, Felicia L., Marks, Natalie C., Hua, Ethan W. +3 more·2015·Nature Communications

Abstract

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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References 37 · Cited by 214

Research works printed but not linked: 1

  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.
Venue
Nature Communications
Published
2015-07-14
Volume
6
Issue
1
Pages
7413-7413
ISSN
2041-1723 (ISSN-L)
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
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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