High-throughput longitudinal electrophysiology screening of mature chamber-specific hiPSC-CMs using optical mapping
Andrew Allan,
Jeffery Creech,
Christian Hausner,
Peyton Krajcarski,
Bianca Gunawan,
Noah Poulin,
Paul Kozlowski,
Christopher Wayne Clark,
Rachel Dow,
Prakaimuk Saraithong,
Devin B. Mair,
Travis Block,
Andre Monteiro da Rocha,
Deok-Ho Kim,
Todd J. Herron
Affiliations
Andrew Allan
Cairn Research, Graveney Road, Faversham, Kent ME13 8UP UK
Jeffery Creech
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA
Christian Hausner
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA
Peyton Krajcarski
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA
Bianca Gunawan
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA
Noah Poulin
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA
Paul Kozlowski
Michigan Medicine, Internal Medicine-Cardiology, Ann Arbor, MI 48109, USA
Christopher Wayne Clark
University of Michigan, School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI 48109, USA
Rachel Dow
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA
Prakaimuk Saraithong
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA; Michigan Medicine, Internal Medicine-Cardiology, Ann Arbor, MI 48109, USA
Devin B. Mair
Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Travis Block
StemBioSys, Inc, 3463 Magic Drive, Suite 110, San Antonio, TX 78229, USA
Andre Monteiro da Rocha
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA; Michigan Medicine, Internal Medicine-Cardiology, Ann Arbor, MI 48109, USA
Deok-Ho Kim
Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Todd J. Herron
University of Michigan, Frankel Cardiovascular Regeneration Core Laboratory, Ann Arbor, MI 48109, USA; Michigan Medicine, Internal Medicine-Cardiology, Ann Arbor, MI 48109, USA; Michigan Medicine, Molecular & Integrative Physiology, Ann Arbor, MI 48109, USA; Corresponding author
Summary: 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.
