Table 3.

Differences Between iPSC-CMs and Adult Human Cardiomyocytes

iPSC-CMsAdult Cardiomyocytes
Morphology
 ShapeRound or polygonalRod and elongated
 Size20–30 μm150 μm
 Nuclei per cellMononucleated≈25% multinucleated
 Multicellular organizationDisorganizedPolarized
 Sarcomere appearanceDisorganizedOrganized
 Sarcomere lengthShorter (≈1.6 μm)Longer (≈2.2 μm)
 Sarcomeric protein – MHCβ>αβ>>α
 Sarcomeric protein – titinN2BAN2B
 Sarcomeric protein – troponin IssTnIcTnI
 Sarcomere units – H zones and A bandsFormed after prolonged differentiationFormed
 Sarcomere units – M bands and T tubulesAbsentPresent
 Distribution of gap junctionsCircumferentialPolarized to intercalated disks
Electrophysiology
 Resting membrane potential≈ –60 mV≈ –90 mV
 Upstroke velocity≈50 V/s≈250 V/s
 AmplitudeSmallLarge
 Spontaneous automaticityExhibitedAbsent
 Hyperpolarization-activated pacemaker (If)PresentAbsent
 Sodium (INa)LowHigh
 Inward rectifier potassium (IK1)Low or absentHigh
 Transient outward potassium current (Ito)InactivatedActivated
 Conduction velocitySlower (≈0.1 m/s)Faster (0.3–1.0 m/s)
Calcium handling
 Ca2+ transientInefficientEfficient
 Amplitudes of Ca2+ transientSmall and decrease with pacingIncrease with pacing
 Excitation-contraction couplingSlowFast
 Contractile force≈nN range/cell≈μN range/cell
 Ca2+-handling proteins (CASQ2, RyR2, and PLN)Low or absentNormal
 Force-frequency relationshipPositiveNegative
Mitochondrial bioenergetics
 Mitochondrial numberLowHigh
 Mitochondrial volumeLowHigh
 Mitochondrial structureIrregular distribution, perinuclearRegular distribution, aligned
 Mitochondrial proteins – DRP1 and OPA1LowHigh
 Metabolic substrateGlycolysis (glucose)Oxidative (fatty acid)
Adrenergic signaling
 Responses to β-adrenergic stimulationLack of inotropic reactionInotropic reaction
 Cardiac α-adrenergic receptor ADRA1AAbsentPresent
  • cTnI indicates cardiac troponin I; iPSC-CMs, induced pluripotent stem cell–derived cardiomyocytes; MHC, myosin heavy chain; and ssTnI, slow skeletal troponin I.

  • Modified from Sayed et al139 with permission from Elsevier. Copyright © 2016, Elsevier.