Cardiac spheroids as promising in vitro models to study the human heart microenvironment
Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and f...
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Veröffentlicht in: | Scientific reports 2017-08, Vol.7 (1), p.7005-12, Article 7005 |
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Sprache: | eng |
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Zusammenfassung: | Three-dimensional
in vitro
cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional
in vitro
models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at ratios approximating those present
in vivo
. The cellular organisation, extracellular matrix and microvascular network mimic human heart tissue. These spheroids have been employed to investigate the dose-limiting cardiotoxicity of the common anti-cancer drug doxorubicin. Viability/cytotoxicity assays indicate dose-dependent cytotoxic effects, which are inhibited by the nitric oxide synthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelial NOS, implicating peroxynitrous acid as a key damaging agent. These data indicate that CSs mimic important features of human heart morphology, biochemistry and pharmacology
in vitro
, offering a promising alternative to animals and standard cell cultures with regard to mechanistic insights and prediction of toxic effects in human heart tissue. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-017-06385-8 |