Modeling Cardiomyopathies in a Dish: State-of-the-Art and Novel Perspectives on hiPSC-Derived Cardiomyocytes Maturation

Abstract

The stem cell technology and the induced pluripotent stem cells (iPSCs) production represent an excellent alternative tool to study cardiomyopathies, which overcome the limitations associated with primary cardiomyocytes (CMs) access and manipulation. CMs from human iPSCs (hiPSC–CMs) are genetically identical to patient primary cells of origin, with the main electrophysiological and mechanical features of CMs. The key issue to be solved is to achieve a degree of structural and functional maturity typical of adult CMs. In this perspective, we will focus on the main differences between fetal-like hiPSC-CMs and adult CMs. A viewpoint is given on the different approaches used to improve hiPSC-CMs maturity, spanning from long-term culture to complex engineered heart tissue. Further, we outline limitations and future developments needed in cardiomyopathy disease modeling.

Optical modulation of excitation-contraction coupling in human-induced pluripotent stem cell-derived cardiomyocytes

“… 29 Secondly, even though the hiPSC-CMs are a consolidated tool and hold an enormous potential in cardiovascular research, their E-C coupling process resembles more the one of fetal/neonatal CMs, thus it is possible that the Ca 2+ clearance machinery in these cells is substantially slower in comparison to adult CMs. 51 , 52 …”

Optical modulation of excitation-contraction coupling in human induced pluripotent stem cell-derived cardiomyocytes

“…First, the experiments were performed at 24°C, a temperature far from the canonical physiological 37°C that could have slowed down the cell behavior (Francesco Lodola et al, 2019). Secondly, even though the hiPSC-CMs are a consolidated tool and hold an enormous potential in cardiovascular research, their E-C coupling process resembles more the one of fetal/neonatal CMs, thus it is possible that the Ca 2+ clearance machinery in these cells is substantially slower in comparison to adult CMs (Kane et al, 2015; Lodola et al, 2021). Conversely, no differences were detected in vehicle treated hiPSC-CMs subjected to the same stimulation protocol ( Figure S5 ).…”