Comparing mouse and human pluripotent stem cell derived cardiac cells: Both systems have advantages for pharmacological and toxicological screening
| Autor: | S M Wu, David A. Elliott, Benjamin Arthur Llewellyn Finnin, John M. Haynes, David A. Anderson, Ebba Louise Lagerqvist, Colin W. Pouton |
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| Rok vydání: | 2015 |
| Předmět: |
Pluripotent Stem Cells
Thapsigargin Cell Survival Cellular differentiation Cell Biology Toxicology Green fluorescent protein Mice chemistry.chemical_compound Calcium imaging Biological Clocks medicine Animals Humans Myocytes Cardiac Doxorubicin Induced pluripotent stem cell Pharmacology Ryanodine receptor Cell Differentiation Anatomy Cell biology Oxygen medicine.anatomical_structure chemistry cardiovascular system medicine.drug |
| Zdroj: | Journal of Pharmacological and Toxicological Methods. 74:17-25 |
| ISSN: | 1056-8719 |
| Popis: | Pluripotent stem cells offer an unparalleled opportunity to investigate cardiac physiology, pharmacology, toxicology and pathophysiology. In this paper we describe the use of both mouse (Nkx2-5(eGFP/w)) and human (NKX2-5(eGFP/w)) pluripotent stem cell reporter lines, differentiated toward cardiac lineage, for live single cell high acquisition rate calcium imaging. We also assess the potential of NKX2-5(eGFP/w) cardiac lineage cells for use toxicological screening as well as establish their sensitivity to a shift between low and high oxygen environments. Differentiated mouse Nkx2-5(eGFP/w) cells demonstrated a wide range of spontaneous oscillation rates that could be reduced by ryanodine (10μM), thapsigargin (1μM) and ZD7288 (10μM). In contrast human NKX2-5(eGFP/w) cell activity was only reduced by thapsigargin (1μM). Human cell survival was sensitive to the addition of trastuzumab and doxorubicin, while the switch from a low to a high oxygen environment affected oscillation frequency. We suggest that the human NKX2-5(eGFP/w) cells are less suitable for studies of compounds affecting cardiac pacemaker activity than mouse Nkx2-5(eGFP/w) cells, but are very suitable for cardiac toxicity studies. |
| Databáze: | OpenAIRE |
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