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Table 1 Summary of methods and relative maturation states of in vitro derived cardiomyocytes

From: Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes

Study Method of differentiation Maturation state achieved and finding
Boheler et al . 2014[139] Monolayer culture High purity hESC- and hiPSC-derived CMs
Cao et al . 2008[59] Suspension EB Expression level of genes encoding structural and force-generating proteins was comparable to fetal heart CMs
Caspi et al . 2009[74] Suspension EB Presence of functional gap junctions
Chan et al . 2013[102] Suspension EB Electrical field stimulation increased expression of cardiac-specific genes
Stimulation promoted a ventricular-like phenotype
Stimulation improved calcium handling
Chung et al . 2007[65] Suspension EB Mitochondrial oxidative metabolism is required for differentiation into a functional cardiac phenotype
Foldes et al . 2011[116] Suspension EB Showed active role for protein kinase signaling in hESC-CM growth and hypertrophy
Gherghiceanu et al . 2011[58] Suspension EB Ultrastructural features of early and immature phenotype:
Myofibrils with sarcomeric pattern
Large glycogen deposits,
Lipid droplets
Ca2+ release units detected on the sarcoplasmic reticulum
Underdeveloped intercalated disks
Spatial location of cells within EBs can affect their phenotype
Cx43 expression not detected
Kamakura et al . 2013[62] Suspension EB Including long-term culture (up to 180 days)
Myofibrils became tightly packed and formed parallel arrays
Appearance of mature Z-, A-, H-, and I-bands
M-bands detected in 360-day-old EBs
Kehat et al . 2004[75] Suspension EB hESC-CM tissue engraftment
Structural and electromechanical connections with NRVMs
Rate-responsive biological pacemaker
Kensah et al . 2013[99] Cardiac bodies Formation of bioartificial cardiac tissue and use of defined animal-free matrix
Kim et al . 2013[83] Suspension EB Induction of adult-like metabolism is critical for establishing disease onset in patient-specific iPSCs
Kim et al . 2010[130] Suspension EB Co-culture with non-cardiomyocytes rescued the arrest of electrophysiological maturation observed following hESC-CM isolation from EBs in early cultures
Purified CMs with a-MHC-PacR
Lundy et al . 2013[60] Monolayer-based direct differentiation Late stage (about 100 days) cells exhibit
organized, longer sarcomeres with aligned Z-disks and organized A- and I-bands
Dense and aligned myofibrils
Higher degree of multinucleation
MYH6 and MYH7 expression level comparable to adult human heart
Improved contraction, Ca2+ handling and AP characteristics
Matsa et al . 2014[133] Suspension EB Allele-specific RNA interference can rescue diseased phenotype in LQTS cardiomyocytes
Moore et al . 2008[71] Suspension EB Cx43 mediates the expression of genes involved in cardiogenesis
Ou et al . 2011[63] Hanging-drop EB Three-dimensional culture and cardiac fibroblast co-culture improved sarcomere organization and Cx43 expression
Pal et al . 2013[64] Suspension EB and monolayer-based direct differentiation Three-dimensional culture increased the expression level of TNNT2
Pekkanen-Mattila et al . 2010[72] Suspension EB, Sparse, irregularly distributed Cx43 expression
END-2 co-culture  
Poon et al . 2013[19] Directed differentiation (suspension EB) Expression level of structural proteins are lower than in fetal ventricular CMs
Purified ventricular phenotype
Sartiani et al . 2007[61] Suspension EB, dissected CMs Electrophysiological characterization over a 3-month period
Maturation approaching an adult phenotype
Thavandiran et al . 2013[101] Suspension EB iPSC-derived engineered cardiac tissue
Combination of a matrix-based microenvironment, uniaxial mechanical stress and a mixture of cells improved engineered cardiac tissue performance
Turnbull et al . 2014[13] Suspension EB Expression of cardiac genes approached levels in adult LV myocardium in engineered cardiac tissues
Xue et al . 2005[76] Suspension EB Functional integration into myocardium
Cell-based pacemaker
Zhang et al . 2013[12] Suspension EB Well-developed sarcomeric structures found in three-dimensional cardiac patches
Upregulated E-C coupling and contractile genes
Zwi et al . 2009[73] Suspension EB Sparse, irregularly distributed Cx43 expression
  1. AP, action potential; CM, cardiomyocyte; Cx43, connexin 43; EB, embryoid body; E-C, excitation-contraction; hESC, human embryonic stem cell; hESC-CM, human embryonic stem cell-derived cardiomyocyte; hiPSC, human induced pluripotent stem cell; iPSC, induced pluripotent stem cell; LQTS, long QT syndrome; LV, left ventricular; NRVM, neonatal rat ventricular myocyte; TNNT2, cardiac troponin T.