Biophysical Stretch Induced Differentiation and Maturation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have emerged as a compelling alternative to primary CMs, which assisted in modeling cardiovascular disease, accelerating drug discovery, exploring the earliest stages of human development, and boosting potential regenerative therapeutics. While it is now feasible to produce human patient- and disease-specific iPSC-CMs at a scalable level with high purity, their fetal-like phenotypes or immaturity is a major hurdle limiting iPSC-CMs’ scientific and preclinical use. Mechanical forces such as static stress, rhythmic contraction, and pulsatile shear stress have been reported to play a primary role in heart development and have been investigated to promote iPSC-CM maturation. In this chapter, we highlight the key distinctions between iPSC-CMs and primary adult CMs and summarized the different biophysical strategies employed to improve the maturation of iPSC-CMs in terms of morphology, contractility, electrophysiology, and metabolism.