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Table 2 Effects of external factors on maturation

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]

  1. AP, action potential; ARVD/C, arrhythmogenic right ventricular dysplasia/cardiomyopathy; Cx43, connexin 43; IGF-1, insulin-like growth factor 1; MAPK, mitogen-activated protein kinase; MDP, maximal diastolic potential; NRVM, neonatal rat ventricular myocyte; TNNT2, cardiac troponin T.