From: Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes
External factors | Effects on developmental maturation | Reference |
---|---|---|
Substrate stiffness/ | Affects differentiation efficiencies. Intermediate-stiffness hydrogels lead to the highest efficiencies | Hazeltine et al. 2014 [97] |
Two/three-dimensional culture | Increases organization of sarcomeric myofilaments | Ou et al. 2011 [63] |
Zhang et al. 2013 [12] | ||
Increases cardiac gene expression | Pal et al. 2013 [64] | |
Turnbull et al. 2014 [13] | ||
Increases contractile and Ca2+ handling protein expression | Tulloch et al. 2011 [10] | |
Zhang et al. 2013 [12] | ||
Promotes alignment and anisotropy | Liau et al. 2011 [66] | |
Promotes functional maturation in general | Christoforou et al. 2013 [67] | |
 | Two-dimensional alignment and groove widths between 30 and 80 μm promote alignment and improve sarcomere structures | Salick et al. 2014 [92] |
Mechanical stimulation | Increases expression of cardiac α-actin and MYH6, and enhances expression of cardiac transcription factors | Gwak et al. 2008 [98] |
Improves tissue morphology and enhances active force levels | Kensah et al. 2013 [99] | |
Increases cell alignment | Tulloch et al. 2011 [10] | |
Schaaf et al. 2011 [11] | ||
Thavandiran et al. 2013 [101] | ||
Zhang et al. 2013 [12] | ||
Increases proliferation rates | Tulloch et al. 2011 [10] | |
Increases AP duration and upstroke velocity, but leads to a less negative MDP | Schaaf et al. 2011 [11] | |
Increases cell size, cytoskeletal assembly and sarcomeric organization | Foldes et al. 2011 [116] | |
 | Cyclic stretch improves TNNT2 and Cx43 expression, increases contraction rates and shortens calcium transients | Mihic et al. 2014 [100] |
Electrical stimulation | Leads to better structured and organized myofilaments | Lieu et al. 2013 [15] |
 | Produces cell elongation, affects expression of a group of cardiac-related genes | Chan et al. 2013 [102] |
Chen et al. 2009 [104] | ||
 | Improves cardiomyocyte alignment, cross-striation patterns and force development | Hirt et al. 2014 [103] |
Energy substrate | Elicits ARVD/C phenotype of increased apoptosis, elevated lipogenesis, and impaired calcium handling in PKP2 mutants | Kim et al. 2013 [83] |
 | Galactose and fatty acids increase oxidative phosphorylation levels, reserve capacity, and maximum respiratory capacity in mitochondria | Rana et al. 2012 [120] |
 | Glucose depletion along with lactose supplementation increase cardiomyocyte purity | Tohyama et al. 2013 [121] |
 | Induction of mitochondrial biogenesis increases cardiomyocyte differentiation | Prowse et al. 2012 [126] |
Other | Stimulating p38-MAPK increases cell size, improves sarcomere and cytoskeletal assembly | Foldes et al. 2011 [116] |
Heineke and Molkentin 2006 [117] | ||
Thyroid hormone increases cardiomyocyte size, sarcomere length, contractile force and anisotropy | Yang et al. 2014 [18] | |
Adrenergic agonists produce hypertrophy | Foldes et al. 2011 [116] | |
 | IGF1 together with electrical or electromechanical stimulation improve NRVM engineered tissue function, SERCA2a and TNNT2 expression | Park et al. 2014 [119] |
 |  | Morgan and Black 2014 [118] |