Engineering spatial-organized cardiac organoids for developmental toxicity testing

Plansky Hoang, Andrew Kowalczewski, Shiyang Sun, Tackla S. Winston, Adriana M. Archilla, Stephanie M. Lemus, A. Gulhan Ercan-Sencicek, Abha R. Gupta, Wenzhong Liu, Maria I. Kontaridis, Jeffrey D. Amack, Zhen Ma

Research output: Contribution to journalArticlepeer-review

Abstract

Emerging technologies in stem cell engineering have produced sophisticated organoid platforms by controlling stem cell fate via biomaterial instructive cues. By micropatterning and differentiating human induced pluripotent stem cells (hiPSCs), we have engineered spatially organized cardiac organoids with contracting cardiomyocytes in the center surrounded by stromal cells distributed along the pattern perimeter. We investigated how geometric confinement directed the structural morphology and contractile functions of the cardiac organoids and tailored the pattern geometry to optimize organoid production. Using modern data-mining techniques, we found that pattern sizes significantly affected contraction functions, particularly in the parameters related to contraction duration and diastolic functions. We applied cardiac organoids generated from 600 μm diameter circles as a developmental toxicity screening assay and quantified the embryotoxic potential of nine pharmaceutical compounds. These cardiac organoids have potential use as an in vitro platform for studying organoid structure-function relationships, developmental processes, and drug-induced cardiac developmental toxicity.

Original languageEnglish (US)
Pages (from-to)1228-1244
Number of pages17
JournalStem Cell Reports
Volume16
Issue number5
DOIs
StatePublished - May 11 2021

Keywords

  • cardiac organoids
  • cell micropatterning
  • data mining
  • embryotoxicity
  • human induced pluripotent stem cells
  • in vitro embryo model

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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