Abstract
Cardiovascular diseases are one of the leading causes of mortality in the western world. Myocardial infarction is among the most prevalent and results in significant cell loss within the myocardium. Similarly, numerous drugs have been identified as having cardiotoxic side effects. The adult human heart is however unable to instigate an effective repair mechanism and regenerate the myocardium in response to such damage. This is in large part due to the withdrawal of cardiomyocytes (CMs) from the cell cycle. Thus, identifying, screening, and developing agents that could enhance the proliferative capacity of CMs holds great potential in cardiac regeneration. Human induced pluripotent stem cells (hiPSCs) and their cardiovascular derivatives are excellent tools in the search for such agents. This chapter outlines state-of-the art techniques for the two-dimensional differentiation and attainment of hiPSC-derived CMs and endothelial cells (ECs). Bioreactor systems and three-dimensional spheroids derived from hiPSC-cardiovascular derivatives are explored as platforms for drug discovery before focusing on relevant assays that can be employed to assess cell proliferation and viability.
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Acknowledgments
The authors thank Ms. S. Tuuli Karhu for the expert advice on the doxorubicin model. The research was co-funded by the Hungarian National Research, Development and Innovation Fund (NKFIA; NVKP-16-1- 2016-0017, “National Heart Program” and 128444), the NIHR Imperial Biomedical Research Centre (BRC), the Medical Research Council (MR/R025002/1), Academy of Finland (grants 321564, 328909), the Finnish Foundation for Cardiovascular Research, Sigrid Jusélius Foundation, University of Helsinki and Drug Research Doctoral Programme.
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Majid, Q.A., Orsolits, B., Pohjolainen, L., Kovács, Z., Földes, G., Talman, V. (2021). Application of Human Induced Pluripotent Stem Cell Technology for Cardiovascular Regenerative Pharmacology. In: Nagy, A., Turksen, K. (eds) Induced Pluripotent Stem (iPS) Cells. Methods in Molecular Biology, vol 2454. Humana, New York, NY. https://doi.org/10.1007/7651_2021_369
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DOI: https://doi.org/10.1007/7651_2021_369
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