2023/03/29 by Fatemeh Kermani, Matías Mosqueira, K. Peters +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Engineering · Neuroscience · #3D Printing in Biomedical Research #Neuroscience and Neural Engineering #Pluripotent Stem Cells Research
paper · pdf · doi:10.1007/s00395-023-00984-5
openalex publication_date 2023/03/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Abstract The prospective use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for cardiac regenerative medicine strongly depends on the electro-mechanical properties of these cells, especially regarding the Ca 2+ -dependent excitation–contraction (EC) coupling mechanism. Currently, the immature structural and functional features of hiPSC-CM limit the progression towards clinical applications. Here, we show that a specific microarchitecture is essential for functional maturation of hiPSC-CM. Structural remodelling towards a cuboid cell shape and induction of BIN1, a facilitator of membrane invaginations, lead to transverse (t)-tubule-like structures. This transformation brings two Ca 2+ channels critical for EC coupling in close proximity, the L-type Ca 2+ channel at the sarcolemma and the ryanodine receptor at the sarcoplasmic reticulum. Consequently, the Ca 2+ -dependent functional interaction of these channels becomes more efficient, leading to improved spatio-temporal synchronisation of Ca 2+ transients and higher EC coupling gain. Thus, functional maturation of hiPSC-cardiomyocytes by optimised cell microarchitecture needs to be considered for future cardiac regenerative approaches.