Membrane remodelling triggers maturation of excitation-contraction coupling in 3D-shaped human-induced pluripotent stem cell-derived cardiomyocytes.
Fatemeh KermaniMatias MosqueiraKyra PetersEnrico D LemmaKleopatra RaptiDirk GrimmMartin BastmeyerMagdalena LaugschMarkus HeckerNina D UllrichPublished in: Basic research in cardiology (2023)
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.
Keyphrases
- high glucose
- endothelial cells
- cell therapy
- room temperature
- protein kinase
- single cell
- left ventricular
- stem cells
- induced pluripotent stem cells
- induced apoptosis
- diabetic rats
- smooth muscle
- drug induced
- mesenchymal stem cells
- pluripotent stem cells
- high resolution
- bone marrow
- oxidative stress
- pi k akt
- signaling pathway
- cell cycle arrest