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A systematized approach to investigate Ca2+ synchronization in iPSC-derived cardiomyocyte networks

Jones, Aled R., Edwards, David Hughes, Cummins, Michael J., Williams, Alan John and George, Christopher H. 2016. A systematized approach to investigate Ca2+ synchronization in iPSC-derived cardiomyocyte networks. Biophysical Journal 110 (3) , 435a. 10.1016/j.bpj.2015.11.2346

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Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have the potential to revolutionize regenerative medicine and drug discovery. However, despite methodological refinement, batch-to-batch reproducibility remains low, and the resulting iPS-CMs exhibit substantial phenotypic variability. Such cellular variegation arises from heterogeneous cell synchronization that is governed by complex modes of cell-to-cell coupling. We developed a systematized approach to investigate the determinants of culture-directed regional Ca2+ intercellular synchronization in iPSC-CM populations. Detailed analysis of the temporal and spatial organization of Ca2+ signals in iPSC-CM matured in embryoid bodies (EB) or ‘on plate’ was used to profile the extent of regional Ca2+ synchronization in iPSC-CM populations over a 4-week period. Early disaggregation of EBs (< 2 weeks) facilitated high levels of spontaneous Ca2+ oscillation and regional synchronization that was not present in the lower number of iPSC-CMs disaggregated from older EBs. All iPSC-CMs lost the capacity to support spontaneous Ca2+ oscillations during ‘on plate’ culture. Notably, two discrete populations of quiescent iPSC-CMs emerged during this period that exhibited differential responses to elevations in extracellular [Ca2+]. The divergent responses of these iPSC-CM populations could be traced back to specific routes of maturation. These studies suggest the feasibility of being able to predictably influence CM phenotype and fate via defined interventions at early stages in the maturation process.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0006-3495
Last Modified: 28 Jun 2019 02:46

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