Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 26, 2022; 10(27): 9588-9601
Published online Sep 26, 2022. doi: 10.12998/wjcc.v10.i27.9588
Human-induced pluripotent stem cell-atrial-specific cardiomyocytes and atrial fibrillation
Wattana Leowattana, Tawithep Leowattana, Pathomthep Leowattana
Wattana Leowattana, Pathomthep Leowattana, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
Tawithep Leowattana, Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand
Author contributions: Leowattana W wrote the paper; Leowattana T and Leowattana P collected the data.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Wattana Leowattana, MD, MSc, PhD, Associate Professor, Professor, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajavithi Road, Rachatawee, Bangkok 10400, Thailand.
Received: May 4, 2022
Peer-review started: May 4, 2022
First decision: June 11, 2022
Revised: June 22, 2022
Accepted: August 16, 2022
Article in press: August 16, 2022
Published online: September 26, 2022

Patient-specific human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) may be produced, genome-edited, and differentiated into multiple cell types for regenerative medicine, disease modeling, drug testing, toxicity screening, and three-dimensional tissue fabrication. There is presently no complete model of atrial fibrillation (AF) available for studying human pharmacological responses and evaluating the toxicity of potential medication candidates. It has been demonstrated that hiPSC-aCMs can replicate the electrophysiological disease phenotype and genotype of AF. The hiPSC-aCMs, however, are immature and do not reflect the maturity of aCMs in the native myocardium. Numerous laboratories utilize a variety of methodologies and procedures to improve and promote aCM maturation, including electrical stimulation, culture duration, biophysical signals, and changes in metabolic variables. This review covers the current methods being explored for use in the maturation of patient-specific hiPSC-aCMs and their application towards a personalized approach to the pharmacologic therapy of AF.

Keywords: Atrial fibrillation, Human-induced pluripotent stem cell-derived atrial cardiomyocytes, Disease modeling, Maturation, Pharmacologic response, Personalized medicine

Core Tip: New medications to treat atrial fibrillation (AF) without causing ventricular arrhythmias are urgently needed. However, access to atrial human tissue is restricted, a problem that may be largely addressed by the general availability of human induced pluripotent stem cell derived atrial cardiomyocytes (hiPSC-aCMs), which provide an excellent opportunity to investigate the pathophysiology of AF and the efficacy and toxicity of treatment options. The primary drawback of using hiPSC-aCMs is their immature phenotype. Several laboratories are researching CM maturation techniques, including culture conditions, electrical stimulation, and biophysical and biochemical features. The current strategies being investigated for use in the maturation of patient-specific hiPSC-aCMs and their application towards a tailored strategy for the pharmacologic management of AF are covered in this review.