Open AccessBioengineering approaches to mature induced pluripotent stem cell-derived atrial cardiomyocytes to model atrial fibrillation
Author(s) -
Olivia T Ly,
Grace E. Brown,
Yong Duk Han,
Dawood Darbar,
Salman R. Khetani
Publication year - 2021
Publication title -
experimental biology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 146
eISSN - 1535-3702
pISSN - 1535-3699
DOI - 10.1177/15353702211009146
Subject(s) - induced pluripotent stem cell , atrial fibrillation , electrophysiology , extracellular matrix , phenotype , neuroscience , human induced pluripotent stem cells , medicine , stem cell , biology , embryonic stem cell , bioinformatics , cardiology , microbiology and biotechnology , gene , genetics
Induced pluripotent stem cells (iPSCs) serve as a robust platform to model several human arrhythmia syndromes including atrial fibrillation (AF). However, the structural, molecular, functional, and electrophysiological parameters of patient-specific iPSC-derived atrial cardiomyocytes (iPSC-aCMs) do not fully recapitulate the mature phenotype of their human adult counterparts. The use of physiologically inspired microenvironmental cues, such as postnatal factors, metabolic conditioning, extracellular matrix (ECM) modulation, electrical and mechanical stimulation, co-culture with non-parenchymal cells, and 3D culture techniques can help mimic natural atrial development and induce a more mature adult phenotype in iPSC-aCMs. Such advances will not only elucidate the underlying pathophysiological mechanisms of AF, but also identify and assess novel mechanism-based therapies towards supporting a more 'personalized' (i.e. patient-specific) approach to pharmacologic therapy of AF.