Stem Cell-Derived Cardiac Spheroids as 3D In Vitro Models of the Human Heart Microenvironment
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.
Keywords3D cultures Bioprinting Cardiovascular regeneration Heart microenvironment Induced pluripotent stem cells Niche Tissue bioengineering Vascularized cardiac spheroid
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.
- 3.Hakkinen KM, Harunaga JS, Doyle AD, Yamada KM (2011) Direct comparisons of the morphology, migration, cell adhesions, and actin cytoskeleton of fibroblasts in four different three-dimensional extracellular matrices. Tissue Eng A 17:713–724. https://doi.org/10.1089/ten.tea.2010.0273 CrossRefGoogle Scholar
- 9.Benam KH, Dauth S, Hassell B et al (2015) Engineered in vitro disease models. Annu Rev Pathol 10:195–262. https://doi.org/10.1146/annurev-pathol-012414-040418 CrossRefPubMedGoogle Scholar