Koivisto, M., Tolvanen, T.A., Toimela, T. et al. Functional human cell-based vascularised cardiac tissue model for biomedical research and testing. Sci Rep 12, 13459 (2022). https://doi.org/10.1038/s41598-022-17498-0
Functional human cell-based vascularised cardiac tissue model for biomedical research and testing
|Author:||Koivisto, Maria1; Tolvanen, Tuomas A.1; Toimela, Tarja1;|
1Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland
2Biocenter Oulu Electron Microscopy Core Facility, University of Oulu, Oulu, Finland
3Computational Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
4Oulu Centre for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 3.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2023020726189
|Publish Date:|| 2023-02-07
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) are widely used in in vitro biomedical research and testing. However, fully matured, adult cardiomyocyte characteristics have not been achieved. To improve the maturity and physiological relevance of hiPSC-derived cardiomyocytes, we co-cultured them with preconstructed vascular-like networks to form a functional, human cell-based cardiac tissue model. The morphology and gene expression profiles indicated advanced maturation in the cardiac tissue model compared to those of a cardiomyocyte monoculture. The cardiac tissue model’s functionality was confirmed by measuring the effects of 32 compounds with multielectrode array and comparing results to human data. Our model predicted the cardiac effects with a predictive accuracy of 91%, sensitivity of 90% and specificity of 100%. The correlation between the effective concentration (EC50) and the reported clinical plasma concentrations was 0.952 (R2 = 0.905). The developed advanced human cell-based cardiac tissue model showed characteristics and functionality of human cardiac tissue enabling accurate transferability of gained in vitro data to human settings. The model is standardized and thus, it would be highly useful in biomedical research and cardiotoxicity testing.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by Business Finland [grant number 6785/31/2017]; Academy of Finland [grant number 310527]; Pirkanmaa Cultural Foundation [grant number 50211545]; Ministry of Agriculture and Forestry [grant number 1149/03.02.05.02/2019]; Juliana von Wendt foundation; and Ministry of Education and Culture. The authors acknowledge the Biocenter Finland (BF), Tampere Imaging Facility (TIF) and Biocenter Oulu (BCO) Electron Microscopy Core Facilities for research infrastructure services.
A gene count matrix with corresponding metadata has been included in supplementary data.
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