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Global Translational Medicine Advancements in cardiac regenerative therapy
Table 1. iPSC-CM maturation and characteristics
Method Approach Maturation Mature CM features Recent Findings
duration (day) (2018 – 2024)
Physical 50 Prolonged culture time 360 (Day 30 as comparison) Prolonged culture
Expanded cellular dimension leads to improved
Sarcomere elongation sarcomere alignment
Reduced rate of beating and functionality. 51
Decreased dual MCL22α/v expression
Greater sarcomere-alignment
Metabolic (hormone Media 7 – 14 Expanded cellular dimension Hormone treatments
treatment) +Triiodothyronine (T3) Reduced roundness significantly enhance
+Glucocorticoid Enhanced MHC-α and SERCA2a cardiac maturation
+Dexamethasone expression markers. 52
Suppressed β-MHC expression
Decline of proliferative activity
Boost in contractile strength and
dynamics
Accelerated calcium signaling
Heightened mitochondrial activity for
energy production
Metabolic (glucose Media ≥3 – ≤20 Expanded cellular dimension Replacement of
replacement) Remove Glucose Reduced roundness glucose with fatty
+palmitate Elongated contractile unit (sarcomere) acids improves
+oleic acid Enhanced mitochondrial quantity and metabolic activity. 53
+carnitine respiratory activity
Boost in contractile strength and
dynamics
Rise of velocity rate and membrane
electrostatic storage
Physical (substrate Substrate stiffness 3 – 9 Regulates sarcomere stress and contractile Stiffer substrates
modification) increase in: activity enhance contractility
polydimethylsiloxane Enhanced force production and structural
(PDMS)/polyacrylic acid More elongated form adoption maturity. 54
(PAA) (6~10 kPa)
Physical (electrical Continuous 4 Enhanced expression of HCN1, MLCV, Electrical stimulation
stimulation) electrical stimulation SCN5A, SERCA, Kv4.3 and GATA4 promotes maturation
(6.6 V/cm and 1 Hz Rise of TNNT cells and improves
+
in 2 ms duration) Cell extension action potential
Ventricular-like action potential characteristics. 55
Increased action potential duration
Improved calcium regulation
In conjunction with mechanical
stimulation through photoactivated PDMS:
amplified surface N-cadherin signaling and
sarcomere contraction
Biochemical/physical CM-fibroblast/MSC 2 × 7 Enhanced contraction speed Co-culture with
co-culture and static- Larger twitch amplitude FB/MSC enhances
cyclic stretching Elevated tensile modulus functional properties
More developed sarcomere architecture of iPSC-CMs. 56
Connexin 43 aggregation
Surface localization of n-cadherin
Reduced cell proliferation capacity
Improved upregulation of MYL2/7 and
MYH7/6 including MLC2, CACNA1C,
NPPA, and SERCA2
Stretching further amplified these effects,
especially with cyclic stress
(Cont’d...)
Volume 4 Issue 1 (2025) 5 doi: 10.36922/gtm.5745
