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Stem Cell-Derived Cardiac Spheroids as 3D In Vitro Models of the Human Heart Microenvironment

  • Madeline Campbell
  • Mamta Chabria
  • Gemma A. Figtree
  • Liudmila Polonchuk
  • Carmine GentileEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2002)

Abstract

Our laboratory has recently developed a novel three-dimensional in vitro model of the human heart, which we call the vascularized cardiac spheroid (VCS). These better recapitulate the human heart’s cellular and extracellular microenvironment compared to the existing in vitro models. To achieve this, human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes, cardiac fibroblasts, and human coronary artery endothelial cells are co-cultured in hanging drop culture in ratios similar to those found in the human heart in vivo. The resulting three-dimensional cellular organization, extracellular matrix, and microvascular network formation throughout the VCS has been shown to mimic the one present in the human heart tissue. Therefore, VCSs offer a promising platform to study cardiac physiology, disease, and pharmacology, as well as bioengineering constructs to regenerate heart tissue.

Keywords

3D cultures Bioprinting Cardiovascular regeneration Heart microenvironment Induced pluripotent stem cells Niche Tissue bioengineering Vascularized cardiac spheroid 

Notes

Acknowledgments

This study was supported by a Postdoctoral Marcus Blackmore Fellowship from the Heart Research Institute and a Kick-Start Grant, a Cardiothoracic Surgery Research Grant Scheme and a CDIP Industry & Community Engagement Fund 2017 from the University of Sydney to CG, by an NHMRC Project Grant (APP1129685) to GF and CG, and by a Roche Post-doctoral Fellowship to MC. We would like to thank Dr. John Russell Brereton (Royal North Shore Hospital, Sydney) for his support, Dr. Christine Chuang (University of Copenhagen) for help with the ECM studies, and Dr. Louise Cole (University of Sydney) for their assistance with confocal imaging.

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Copyright information

© Springer Science+Business Media New York 2018

Authors and Affiliations

  • Madeline Campbell
    • 1
  • Mamta Chabria
    • 2
  • Gemma A. Figtree
    • 1
  • Liudmila Polonchuk
    • 2
  • Carmine Gentile
    • 1
    • 3
    • 4
    Email author
  1. 1.Sydney Medical SchoolUniversity of SydneySydneyAustralia
  2. 2.Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.BaselSwitzerland
  3. 3.Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  4. 4.Kolling Institute, Royal North Shore HospitalSydneyAustralia

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