Cardiac spheroids as promising in vitro models to study the human heart microenvironment
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Cardiac spheroids as promising in vitro models to study the human heart microenvironment. / Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura; Hoflack, Jean-Christophe; Figtree, Gemma A; Davies, Michael J; Gentile, Carmine.
In: Scientific Reports, Vol. 7, 7005, 01.08.2017.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Cardiac spheroids as promising in vitro models to study the human heart microenvironment
AU - Polonchuk, Liudmila
AU - Chabria, Mamta
AU - Badi, Laura
AU - Hoflack, Jean-Christophe
AU - Figtree, Gemma A
AU - Davies, Michael J
AU - Gentile, Carmine
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-017-06385-8
DO - 10.1038/s41598-017-06385-8
M3 - Journal article
C2 - 28765558
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 7005
ER -
ID: 182331016