Abstract
Cardiac arrhythmias can arise due to a host of both genetic and acquired factors. Specifically, the genetic basis of arrhythmogenesis is not fully understood due to the lack of robust models that reliably recapitulate human physiology. Human-induced pluripotent stem cells (hiPSCs) have strengthened regenerative medicine by producing cells that bear the genetic signature of patients being studied. Upon differentiation into hiPSC-derived cardiomyocytes (hiPSC-CMs), these cells can be used to phenotype known mutations or suspected variants that may contribute to abnormal electrical activity in the heart. Furthermore, novel therapeutics can be screened for the management and treatment of arrhythmias in patient-specific hiPSC-CMs. In this chapter, we will briefly discuss the practical utility of hiPSC-CMs to study inherited arrhythmias with a specific focus on atrial fibrillation (AF), catecholaminergic polymorphic ventricular tachycardia (CPVT), and disruptive electrical events that may occur in patients with hypertrophic cardiomyopathy (HCM). We will describe an investigative pipeline that integrates genome editing, tissue engineering, biobanking, and systems biology as complementary approaches. Together, these various applications are directed toward a common goal of bench-to-bedside characterization of arrhythmias in patient-specific hiPSC-CMs.
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Abbreviations
- AF:
-
Atrial fibrillation
- AFM:
-
Atomic force microscopy
- CiPA:
-
Comprehensive in vitro proarrhythmia assay
- DCM:
-
Dilated cardiomyopathy
- ddPCR:
-
Droplet digital polymerase chain reaction
- ER:
-
Endoplasmic reticulum
- FFA:
-
Free fatty acids
- FFT:
-
Fast Fourier transform
- GECI:
-
Genetically encoded calcium indicator
- GEVI:
-
Genetically encoded voltage indicator
- GWAS:
-
Genome-wide association studies
- HCM:
-
Hypertrophic cardiomyopathy
- hESCs:
-
Human embryonic stem cells
- hiPSC-CMs:
-
Human-induced pluripotent stem cell-derived cardiomyocytes
- hiPSCs:
-
Human-induced pluripotent stem cells
- LQTS:
-
Long QT syndrome
- LTCC:
-
L-type calcium channel
- MEA:
-
Multielectrode array
- M-MLV:
-
Modified Moloney leukemia virus
- MS:
-
Mass spectrometry
- PBMCs:
-
Peripheral blood mononuclear cells
- pegRNA:
-
Prime editing guide RNA
- PTM:
-
Posttranslational modification
- QC:
-
Quality control
- qPCR:
-
Quantitative polymerase chain reaction
- RyR:
-
Ryanodine receptor
- SCD:
-
Sudden cardiac death
- SNP:
-
Single nucleotide polymorphism
- SR:
-
Sarcoplasmic reticulum
- TEM:
-
Transmission electron microscopy
- TTs:
-
T-tubules
- VF:
-
Ventricular fibrillation
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Lin, L., Barszczewski, T., Burgon, P.G., Tibbits, G.F. (2022). Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform for Modeling Arrhythmias. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_44-1
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