Atrial-specific hiPSC-derived cardiomyocytes in drug discovery and disease modeling.

Autor: Gharanei M; Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; hiPSC-CM Research Team, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada., Shafaattalab S; Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; hiPSC-CM Research Team, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada., Sangha S; Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; hiPSC-CM Research Team, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada., Gunawan M; Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; hiPSC-CM Research Team, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada., Laksman Z; Department of Medicine, University of British Columbia, Vancouver, BC, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada., Hove-Madsen L; Cardiac Rhythm and Contraction Group, IIBB-CSIC, CIBERCV, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain., Tibbits GF; Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; hiPSC-CM Research Team, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada. Electronic address: tibbits@sfu.ca.
Jazyk: angličtina
Zdroj: Methods (San Diego, Calif.) [Methods] 2022 Jul; Vol. 203, pp. 364-377. Date of Electronic Publication: 2021 Jun 16.
DOI: 10.1016/j.ymeth.2021.06.009
Abstrakt: The discovery and application of human-induced pluripotent stem cells (hiPSCs) have been instrumental in the investigation of the pathophysiology of cardiovascular diseases. Patient-specific hiPSCs can now be generated, genome-edited, and subsequently differentiated into various cell types and used for regenerative medicine, disease modeling, drug testing, toxicity screening, and 3D tissue generation. Modulation of the retinoic acid signaling pathway has been shown to direct cardiomyocyte differentiation towards an atrial lineage. A variety of studies have successfully differentiated patient-specific atrial cardiac myocytes (hiPSC-aCM) and atrial engineered heart tissue (aEHT) that express atrial specific genes (e.g., sarcolipin and ANP) and exhibit atrial electrophysiological and contractility profiles. Identification of protocols to differentiate atrial cells from patients with atrial fibrillation and other inherited diseases or creating disease models using genetic mutation studies has shed light on the mechanisms of atrial-specific diseases and identified the efficacy of atrial-selective pharmacological compounds. hiPSC-aCMs and aEHTs can be used in drug discovery and drug screening studies to investigate the efficacy of atrial selective drugs on atrial fibrillation models. Furthermore, hiPSC-aCMs can be effective tools in studying the mechanism, pathophysiology and treatment options of atrial fibrillation and its genetic underpinnings. The main limitation of using hiPSC-CMs is their immature phenotype compared to adult CMs. A wide range of approaches and protocols are used by various laboratories to optimize and enhance CM maturation, including electrical stimulation, culture time, biophysical cues and changes in metabolic factors.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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