TABLE 1.
Summary of studies carried out using hiPSC-CMs in ACM and associated discoveries.
| Variant | Culture method | Findings | Highlights | Reference |
|---|---|---|---|---|
| PKP2 c.1841T>C | Embryoid Body (EB) | • Decreaseddesmosome gene expression | • ACM phenotype | Ma et al. (2013) |
| • Lipid droplets accumulation | •Lipogenesis | |||
| PKP2 c.972InsT/N | EB | • Reduced density in desmosomes | • ACM phenotype | Caspi et al. (2013) |
| • Distorted desmosomes | • Lipogenesis | |||
| • Lipid droplets accumulation | ||||
| PKP2 c.2484C>T | EB | • JUP nuclear translocation | • Transdifferentiation | Kim et al. (2013) |
| • Decreased β-catenin activity | ||||
| • Increased PPARγ activity | ||||
| PKP2 c.2484C>T c.2013delC | EB | • Cardiomyocytes apoptosis | • Transdifferentiation | Wen et al. (2015) |
| • Lipid droplets accumulation | ||||
| • Co-activation of PPARγ and PPARα | ||||
| PKP2 c.2013delC | Monolayer | • hiPSC differentiation in epicardial cells | • Transdifferentiation | Kohela et al. (2021) |
| • Spontaneous fibro-fatty cellular differentiation | • Epicardial cells differentiation into fibroblasts and fat cells | |||
| DSG2 p.Gly638Arg | EB | • Lower upstroke in AP | • Electrophysiological remodeling | El-Battrawy et al. (2018) |
| • Increase IKr current | ||||
| • More sensitive to Isoprenaline | ||||
| DSP | • Lower amplitude of INa and ICaL currents | • Electrophysiological remodeling | Gusev et al. (2020) | |
| H1684R | • Higher Ito current | |||
| • Shortened AP | ||||
| PKP2 c.354delT | • Decreased Wnt/β catenin activity | • Electrophysiological remodeling | Khudiakov et al. (2020) | |
| • Decreased INa current | • Wnt/β catenin regulates INa current density | |||
| PKP2 Truncating PKP2 mutation by CRISPR-Cas9 | Monolayer | • Aberrant expression and localization of junctional components | • Sarcomeric disorganization | Zhang J et al. (2021) |
| • Destabilization of sarcomere | • Electrophysiological remodeling | |||
| • Increased in APD | • Contractile defect | |||
| DSG2 c.2358delA | • Increase in pro-inflammatory cytokine expression | • Inflammatory | Hawthorne et al. (2021) | |
| • Shortened AP | • Electrophysiological remodeling | |||
| • Shortened Ca2+ transients | • Ca2+ handling perturbation | |||
| PKP2 | Monolayer | • Impaired desmosome assembly | • Contractile defect | Inoue et al. (2022) |
| • Disruption of Intercalated disc | ||||
| • Decrease in the contractile function | ||||
| DSC2 c.394C>T | Monolayer | • Decrease of INa current | • Electrical instability | Moreau et al. (2021) |
| • Increase of global IK current | • AAD therapy (Sotalol and Flecainide) | |||
| • Shortened AP | ||||
| PKP2 c.2013delC | monolayer | • Pro-inflammation | • New potential signaling targeting NF-κB | Chelko et al. (2019) |
| • Inhibition of NF-κB rescue | ||||
| DSC2 c.394C>T | Monolayer | • Electrophysiological and calcium abnormalities rescued by PPARγ inhibition (T0070907) | • New signaling pathway implications in electrophysiological and contractile defects | Reisqs et al. (2022) |
| DSC2 c.394C>T | Monolayer | • Electrophysiological and calcium abnormalities rescued by an anti-diuretic (Spironolactone) | • New potential therapeutic strategy by Spironolactone | Reisqs et al. (2023) |
| PLN R14del | • New hiPSC Generation | Vera et al. (2022) | ||
| DSP c.1386del | • New hiPSC Generation | Loiben et al. (2023) | ||
| DSP c.6687delA | EHT | • Structural and contractile defect | • 3D culture | Bliley et al. (2021) |