Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.
The advancement of human induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs. Exogenous electrical stimulation provides a biomimetic pacemaker-like stimuli that has been shown to advance the electrical properties of tissue engineered cardiac constructs. Recently, we demonstrated that the incorporation of electrically conductive silicon nanowires to hiPSC cardiac spheroids led to advanced structural and functional development of hiPSC-CMs by improving the endogenous electrical microenvironment. Here, we reasoned that the enhanced endogenous electrical microenvironment of nanowired hiPSC cardiac spheroids would synergize with exogenous electrical stimulation to further advance the functional development of nanowired hiPSC cardiac spheroids. For the first time, we report that the combination of nanowires and electrical stimulation enhanced cell-cell junction formation, improved development of contractile machinery, and led to a significant decrease in the spontaneous beat rate of hiPSC cardiac spheroids. The advancements made here address critical challenges for the use of hiPSC-CMs in cardiac developmental and translational research and provide an advanced cell delivery vehicle for the next generation of cardiac repair.
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Dylan J
DJ
Richards
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Yu
Y
Tan
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Robert
R
Coyle
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Yang
Y
Li
Department of Chemistry, the James Franck Institute and the Institute for Biophysical Dynamics, The University of Chicago , Chicago, Illinois 60637, United States.
Ruoyu
R
Xu
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Nelson
N
Yeung
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Arran
A
Parker
Donald R
DR
Menick
Department of Chemistry, the James Franck Institute and the Institute for Biophysical Dynamics, The University of Chicago , Chicago, Illinois 60637, United States.
Bozhi
B
Tian
Bioengineering Department, Clemson University , Clemson, South Carolina 29634, United States.
Ying
Y
Mei
D002454:Cell Differentiation; D002478:Cells, Cultured; D004558:Electric Stimulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D053770:Nanowires; D012825:Silicon
D012825:Silicon
Silicon nanowires; cardiac spheroids; electrical stimulation; human induced pluripotent stem cell-derived cardiomyocytes