Maturation of human pluripotent stem cell derived cardiomyocytes is improved in cardiovascular construct
| Autor: | Katriina Aalto-Setälä, Jertta-Riina Sarkanen, Hanna Vuorenpää, Timo Ylikomi, Mari Pekkanen-Mattila, Kirsi Penttinen, Tuula Heinonen |
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| Přispěvatelé: | Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, University of Tampere |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stromal cell Vascular-like network Clinical Biochemistry Biomedical Engineering Bioengineering Biology Umbilical vein Biokemia solu- ja molekyylibiologia - Biochemistry cell and molecular biology 03 medical and health sciences Foreskin Lääketieteen bioteknologia - Medical biotechnology Maturation medicine Induced pluripotent stem cell Ion channel Calcium metabolism Cardiomyocytes Cell Biology Anatomy In vitro Cell biology Electrophysiology 030104 developmental biology medicine.anatomical_structure Original Article Biotechnology |
| Zdroj: | Cytotechnology |
| ISSN: | 0920-9069 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1007/s10616-017-0088-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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