Self-organizing human cardiac microchambers mediated by geometric confinement

Zhen Ma, Jason Wang, Peter Loskill, Nathaniel Huebsch, Sangmo Koo, Felicia L. Svedlund, Natalie C. Marks, Ethan W. Hua, Costas P. Grigoropoulos, Bruce R. Conklin () and Kevin E. Healy ()
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Zhen Ma: University of California
Jason Wang: University of California
Peter Loskill: University of California
Nathaniel Huebsch: Gladstone Institute of Cardiovascular Disease
Sangmo Koo: University of California
Felicia L. Svedlund: University of California
Natalie C. Marks: University of California
Ethan W. Hua: Gladstone Institute of Cardiovascular Disease
Costas P. Grigoropoulos: University of California
Bruce R. Conklin: Gladstone Institute of Cardiovascular Disease
Kevin E. Healy: University of California

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8413

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