In:
Basic Research in Cardiology, Springer Science and Business Media LLC, Vol. 118, No. 1 ( 2023-03-29)
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.
Type of Medium:
Online Resource
ISSN:
1435-1803
DOI:
10.1007/s00395-023-00984-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
1458470-0
Permalink