title: Maturation of human pluripotent stem cell derived cardiomyocytes is improved in cardiovascular construct.
abstract: In order to translate preclinical data into the clinical studies, relevant in vitro models with structure and key functional properties similar to native human tissue should be used. In vitro cardiac models with vascular structures mimic the highly vascularized myocardium and provide interactions between endothelial cells, stromal cells and cardiomyocytes. Currently, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been shown to present immature morphology and fetal-like electrophysiological properties that may limit their use as physiological test platform. The aim of this study was to develop multicellular in vitro cardiovascular construct modeling human heart tissue. In the cardiovascular construct, hPSC-CMs were cultured with a vascular-like network formed by human foreskin fibroblasts and human umbilical vein endothelial cells that served as a platform in the construct. Cardiomyocyte orientation, maturation, electrophysiological properties and drug responses of the cardiovascular construct were characterized and compared to CM monoculture. hPSC-CMs in cardiovascular construct showed elongated morphology and aligned with the vascular-like network. Electrophysiological properties and calcium metabolism of hPSC-CMs as well as response to E-4031 and adrenaline demonstrated normal physiological behavior. Increased expression of cardiac structural proteins and ion channels in cardiovascular construct compared to CM monoculture were detected. In conclusion, vascular-like network supports the structural and functional maturation of hPSC-CMs. Our results suggest that cardiovascular construct presents more mature in vitro cardiac model compared to CM monoculture and could therefore serve as an advanced test system for cardiac safety and efficacy assessment as well as a model system for biomedical research.
authors.affiliation: FICAM, Finnish Centre for Alternative Methods, Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Vuorenpää
authors.affiliation: BioMediTech, Institute of Biomedical Technology, Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland. kirsi.penttinen@uta.fi.|Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland. kirsi.penttinen@uta.fi.
authors.forename: Kirsi
authors.identifier: http://orcid.org/0000-0003-1925-6420
authors.initials: K
authors.lastname: Penttinen
authors.affiliation: FICAM, Finnish Centre for Alternative Methods, Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Heinonen
authors.affiliation: BioMediTech, Institute of Biomedical Technology, Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Pekkanen-Mattila
authors.affiliation: Department of Cell Biology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
authors.forename: Jertta-Riina
authors.initials: JR
authors.lastname: Sarkanen
authors.affiliation: FICAM, Finnish Centre for Alternative Methods, Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.|Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.|Department of Cell Biology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Ylikomi
authors.affiliation: BioMediTech, Institute of Biomedical Technology, Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.|Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.|Heart Hospital, Tampere University Hospital, Tampere, Finland.
authors.forename: Katriina
authors.initials: K
authors.lastname: Aalto-Setälä
keywords: Cardiomyocytes; Maturation; Vascular-like network