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 | Â | |
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 |