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Action potential variability in human pluripotent stem cell-derived cardiomyocytes obtained from healthy donors

Carvalho, A B ; Coutinho, Keyla Cristiny da Silva ; Barbosa, Raiana Andrade Quintanilha ; de Campos, Dilza Balteiro Pereira ; Leitão, Isabela de Carvalho ; Pinto, R S ; Dos Santos, D Silva ; Farjun, Bruna ; De Araújo, Dayana da Silva ; Mesquita, Fernanda Cristina Paccola ; Monnerat-Cahli, G ; Medei, E H ; Kasai-Brunswick, Tais Hanae ; De Carvalho, A C Campos

Frontiers in physiology, 2022-12, Vol.13, p.1077069-1077069 [Periódico revisado por pares]

Switzerland: Frontiers Media S.A

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  • Título:
    Action potential variability in human pluripotent stem cell-derived cardiomyocytes obtained from healthy donors
  • Autor: Carvalho, A B ; Coutinho, Keyla Cristiny da Silva ; Barbosa, Raiana Andrade Quintanilha ; de Campos, Dilza Balteiro Pereira ; Leitão, Isabela de Carvalho ; Pinto, R S ; Dos Santos, D Silva ; Farjun, Bruna ; De Araújo, Dayana da Silva ; Mesquita, Fernanda Cristina Paccola ; Monnerat-Cahli, G ; Medei, E H ; Kasai-Brunswick, Tais Hanae ; De Carvalho, A C Campos
  • Assuntos: action potential (AP) ; cardiomyocytes ; cell lines ; differentiation methods ; iPSC (induced pluripotent stem cell) ; Physiology ; variability
  • É parte de: Frontiers in physiology, 2022-12, Vol.13, p.1077069-1077069
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    Reviewed by: Jean-Sebastien Rougier, University of Bern, Switzerland
    This article was submitted to Cardiac Electrophysiology, a section of the journal Frontiers in Physiology
    Edited by: Flavien Charpentier, INSERM U1087 Institut du Thorax, France
    Mark Hoogendijk, Erasmus Medical Center, Netherlands
  • Descrição: Human pluripotent stem cells (PSC) have been used for disease modelling, after differentiation into the desired cell type. Electrophysiologic properties of cardiomyocytes derived from pluripotent stem cells are extensively used to model cardiac arrhythmias, in cardiomyopathies and channelopathies. This requires strict control of the multiple variables that can influence the electrical properties of these cells. In this article, we report the action potential variability of 780 cardiomyocytes derived from pluripotent stem cells obtained from six healthy donors. We analyze the overall distribution of action potential (AP) data, the distribution of action potential data per cell line, per differentiation protocol and batch. This analysis indicates that even using the same cell line and differentiation protocol, the differentiation batch still affects the results. This variability has important implications in modeling arrhythmias and imputing pathogenicity to variants encountered in patients with arrhythmic diseases. We conclude that even when using isogenic cell lines to ascertain pathogenicity to variants associated to arrythmias one should use cardiomyocytes derived from pluripotent stem cells using the same differentiation protocol and batch and pace the cells or use only cells that have very similar spontaneous beat rates. Otherwise, one may find phenotypic variability that is not attributable to pathogenic variants.
  • Editor: Switzerland: Frontiers Media S.A
  • Idioma: Inglês
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