Abstract
Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells, are abundant sources of cardiomyocytes (CMs) for cell replacement therapy and other applications such as disease modeling, drug discovery and cardiotoxicity screening. However, hPSC-derived CMs display immature structural, electrophysiological, calcium-handling and metabolic properties. Here, we review various biological as well as physical and topographical cues that are known to associate with the development of native CMs in vivo to gain insights into the development of strategies for facilitated maturation of hPSC-CMs.
Highlights
Despite advances in treatment, cardiovascular diseases continue to be the leading cause of death worldwide
Human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, can propagate indefinitely while maintaining their ability to differentiate into virtually all cell types, including CMs
By measuring thapsigargin- and tetracaine-sensitive Ca2+ sparks as the fundamental events of Ca2+ handling, we directly demonstrated that calcium-induced calcium release is functional in Human pluripotent stem cell (hPSC)-CMs [33]
Summary
Cardiovascular diseases continue to be the leading cause of death worldwide. Electrical conditioning robustly led to many aspects of cellular maturation of hESC-CMs, including electrophysiological maturation without phase 4depolarization similar to Kir2.1 gene transfer, Ca2+-handing maturation with increased peak Ca2+ transient amplitude and SR Ca2+ load, and structured organization of myofilaments, as well as upregulation of contractile and t-tubule biogenesis proteins [97]. With better understanding of the developmental cues leading to maturation of hPSC-CMs, as well as recent advances in fabrication of two-dimensional and three-dimensional culture substrates, strategies to facilitate maturation of these cells can be developed This would enable the use of both hESC-CMs and human iPSC-CMs as safe and efficient sources for cell and tissue replacement therapy for the treatment of heart disease. Competing interests The authors declare that they have no competing interests
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
