TY - JOUR
T1 - High-throughput longitudinal electrophysiology screening of mature chamber-specific hiPSC-CMs using optical mapping
AU - Allan, Andrew
AU - Creech, Jeffery
AU - Hausner, Christian
AU - Krajcarski, Peyton
AU - Gunawan, Bianca
AU - Poulin, Noah
AU - Kozlowski, Paul
AU - Clark, Christopher Wayne
AU - Dow, Rachel
AU - Saraithong, Prakaimuk
AU - Mair, Devin B.
AU - Block, Travis
AU - Monteiro da Rocha, Andre
AU - Kim, Deok Ho
AU - Herron, Todd J.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/7/21
Y1 - 2023/7/21
N2 - hiPSC-CMs are being considered by the Food and Drug Administration and other regulatory agencies for in vitro cardiotoxicity screening to provide human-relevant safety data. Widespread adoption of hiPSC-CMs in regulatory and academic science is limited by the immature, fetal-like phenotype of the cells. Here, to advance the maturation state of hiPSC-CMs, we developed and validated a human perinatal stem cell-derived extracellular matrix coating applied to high-throughput cell culture plates. We also present and validate a cardiac optical mapping device designed for high-throughput functional assessment of mature hiPSC-CM action potentials using voltage-sensitive dye and calcium transients using calcium-sensitive dyes or genetically encoded calcium indicators (GECI, GCaMP6). We utilize the optical mapping device to provide new biological insight into mature chamber-specific hiPSC-CMs, responsiveness to cardioactive drugs, the effect of GCaMP6 genetic variants on electrophysiological function, and the effect of daily β-receptor stimulation on hiPSC-CM monolayer function and SERCA2a expression.
AB - hiPSC-CMs are being considered by the Food and Drug Administration and other regulatory agencies for in vitro cardiotoxicity screening to provide human-relevant safety data. Widespread adoption of hiPSC-CMs in regulatory and academic science is limited by the immature, fetal-like phenotype of the cells. Here, to advance the maturation state of hiPSC-CMs, we developed and validated a human perinatal stem cell-derived extracellular matrix coating applied to high-throughput cell culture plates. We also present and validate a cardiac optical mapping device designed for high-throughput functional assessment of mature hiPSC-CM action potentials using voltage-sensitive dye and calcium transients using calcium-sensitive dyes or genetically encoded calcium indicators (GECI, GCaMP6). We utilize the optical mapping device to provide new biological insight into mature chamber-specific hiPSC-CMs, responsiveness to cardioactive drugs, the effect of GCaMP6 genetic variants on electrophysiological function, and the effect of daily β-receptor stimulation on hiPSC-CM monolayer function and SERCA2a expression.
KW - Cell biology
KW - Medicine
KW - Screening in health technology
UR - http://www.scopus.com/inward/record.url?scp=85162977615&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85162977615&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.107142
DO - 10.1016/j.isci.2023.107142
M3 - Article
C2 - 37416454
AN - SCOPUS:85162977615
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 7
M1 - 107142
ER -