Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

作者：Kosmidis Georgios; Bellin Milena; Ribeiro Marcelo C; van Meer Berend; Ward van Oostwaard Dorien; Passier Robert; Tertoolen Leon G J; Mummery Christine L; Casini Simona

来源：Biochemical and Biophysical Research Communications, 2015, 467(4): 998-1005.

DOI：10.1016/j.bbrc.2015.10.026

• Human embryonic stem cells
• Cardiomyocytes
• Glucocorticoids
• Calcium handling
• Electrophysiology

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.

• 出版日期2015-11-27