Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Ohio State University
  • University of Kansas

Details

Original languageEnglish (US)
Article number13188
JournalScientific reports
Volume9
Issue number1
StatusPublished - Dec 1 2019
Peer-reviewedYes

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed for cardiac cell transplantation studies more than a decade ago. In order to establish the hiPSC-CM-based platform as an autologous source for cardiac repair and drug toxicity, it is vital to understand the functionality of cardiomyocytes. Therefore, the goal of this study was to assess functional physiology, ultrastructural morphology, gene expression, and microRNA (miRNA) profiling at Wk-1, Wk-2 & Wk-4 in hiPSC-CMs in vitro. Functional assessment of hiPSC-CMs was determined by multielectrode array (MEA), Ca2+ cycling and particle image velocimetry (PIV). Results demonstrated that Wk-4 cardiomyocytes showed enhanced synchronization and maturation as compared to Wk-1 & Wk-2. Furthermore, ultrastructural morphology of Wk-4 cardiomyocytes closely mimicked the non-failing (NF) adult human heart. Additionally, modulation of cardiac genes, cell cycle genes, and pluripotency markers were analyzed by real-time PCR and compared with NF human heart. Increasing expression of fatty acid oxidation enzymes at Wk-4 supported the switching to lipid metabolism. Differential regulation of 12 miRNAs was observed in Wk-1 vs Wk-4 cardiomyocytes. Overall, this study demonstrated that Wk-4 hiPSC-CMs showed improved functional, metabolic and ultrastructural maturation, which could play a crucial role in optimizing timing for cell transplantation studies and drug screening.

Citation formats

APA

Kumar, N., Dougherty, J. A., Manring, H. R., Elmadbouh, I., Mergaye, M., Czirok, A., ... Khan, M. (2019). Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes. Scientific reports, 9(1), [13188]. https://doi.org/10.1038/s41598-019-49653-5

Harvard

Kumar, N, Dougherty, JA, Manring, HR, Elmadbouh, I, Mergaye, M, Czirok, A, Greta Isai, D, Belevych, AE, Yu, L, Janssen, PML, Fadda, P, Gyorke, S, Ackermann, MA, Angelos, MG & Khan, M 2019, 'Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes', Scientific reports, vol. 9, no. 1, 13188. https://doi.org/10.1038/s41598-019-49653-5