Journal: bioRxiv

Article Title: Nutrient-dependent pathology in mitochondrial hypertrophic cardiomyopathy model

doi: 10.1101/2025.09.24.678132

Figure Lengend Snippet: Generation and characterization of iPSC-derived cardiomyocytes. A. Schematic overview of the experimental design. B. Reprogramming factor expression in control and MRPL44 patient-derived iPSCs after reprogramming (OCT4; green, NANOG; red and TRA-1-60; green) (Scale bar; 200µm) C. Cardiac marker positivity of iPSC derived CMs. Immunofluorescence, cardiac troponin (cTnT; green) and nuclei (DAPI, blue) (Scale bar; 50 µm). D. Purification of iPSC derived cardiomyocytes. Representative FACS analysis shows 91.9% cTnT positive cells after purification.

Article Snippet: Contracting cells were observed from day 8 onwards. iPSC derived CMs were purified using magnetic beads as per manufacturer’s instructions (#130-110-188, Miltenyi Biotec) on day 15-20 of differentiation.

Techniques: Derivative Assay, Expressing, Control, Marker, Immunofluorescence, Purification

Journal: bioRxiv

Article Title: Nutrient-dependent pathology in mitochondrial hypertrophic cardiomyopathy model

doi: 10.1101/2025.09.24.678132

Figure Lengend Snippet: Impaired lipid homeostasis in patient CMs A. Lipid droplet analysis. Immunostaining of neutral lipid droplets in MRPL44 and Control iPSC-CMs by Lipidtox. (cTnT, yellow; Lipidtox, red; TOM20, green; DAPI, blue; scale: 50 µm) B. Quantification of droplets per cell between patient and control CMs. (n=1273 CMs) *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 (Student’s t-test) C. Gene expression levels of lipid transporter CD36, LDLR, ACSL1 and PDK4 gene in different media conditions. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 (Wald test)

Article Snippet: Contracting cells were observed from day 8 onwards. iPSC derived CMs were purified using magnetic beads as per manufacturer’s instructions (#130-110-188, Miltenyi Biotec) on day 15-20 of differentiation.

Techniques: Immunostaining, Control, Gene Expression

Journal: JACC. Clinical electrophysiology

Article Title: Toward Digital Twin Technology for Precision Pharmacology

doi: 10.1016/j.jacep.2023.10.024

Figure Lengend Snippet: (A) Comparison of predicted effects of drugs on experimentally recorded iCell induced pluripotent stem cell–derived cardiomyocyte (iPSC-CM) action potential duration at 90% repolarization rate (APD90) and digital-twin iPSC-CM APD90. We constructed 205 digital-twin iCell iPSC-CMs by randomly varying within the SDs of the experimental measurements. (B) Comparison of simulated iPSC-CM ΔAPD90 to experimentally recorded iPSC-CMs for moxifloxacin (Mox) concentrations ranging from 10 to 70 μM (left) and a range of dofetilide (Dof) concentrations (0.5-4 nM). Example action potentials (APs) demonstrating the effect of moxifloxacin and dofetilide on AP morphology and duration from iCell digital twins are also shown. (C) Experiments (purple) and digital twins (blue) of a long-QT syndrome type 1 (LQT1) mutation. , (D) LQT1 example traces with early afterdepolarizations after 140 μM moxifloxacin and 4 nM dofetilide. APD = action potential duration; APD90cF = Fridericia-corrected action potential duration at 90% repolarization rate; Sims = simulations.

Article Snippet: The model is derived from iCell Cardiomyocyte (cell line 01434) iPSC-CMs.

Techniques: Comparison, Derivative Assay, Construct, Mutagenesis

Journal: JACC. Clinical electrophysiology

Article Title: Toward Digital Twin Technology for Precision Pharmacology

doi: 10.1016/j.jacep.2023.10.024

Figure Lengend Snippet: Shown is electric activity for a multiring, 1-dimensional digital tissue twin model comprising 1,019 induced pluripotent stem cell–derived cardiomyocyte digital twins connected by resistances to simulate gap junctions with 100 spontaneous beating cells driving depolarization. Each simulated tissue contained identical patterns of randomized spatial heterogeneity imposed by randomly varying within the SDs of the experimental measurements. (A) Prediction of control case in the absence of drug (n = 10 simulations). (B) Predicted effect of the application of 2 nM dofetilide (Dof) (n = 10 simulations). (C) Application of 10 μM moxifloxacin (Mox) (10 simulations). The bar graphs on the right show proxy metrics for cardiac cycle length (left bars) and dispersion of repolarization (right bars; maximum – minimum cardiac cycle).

Article Snippet: The model is derived from iCell Cardiomyocyte (cell line 01434) iPSC-CMs.

Techniques: Activity Assay, Derivative Assay, Control, Dispersion