1. A Physiologically-relevant and Screening-ready, Human iPSC-derived Cardiomyocyte
Platform
Presented by: Fabian Zanella, StemoniX
Authors: Zanella, Fabian, StemoniX; Contu, Riccardo, StemoniX; Spangenberg, Stephan,
StemoniX; Si, Wonjong, StemoniX; Selke, Janet, StemoniX; Peris, Matthew, StemoniX; Gordon,
Ryan, StemoniX; Yeh, Ping, StemoniX; Petcavich, Robert, StemoniX
Abstract:
Human induced pluripotent stem cells (hiPSCs) have been perceived as a powerful tool to study
organ and system-specific diseases and toxicity. hiPSC-derived cardiomyocytes have been
increasingly adopted in cardiac disease modeling and cardiotoxicity research. Despite their
inarguable value in current research pipelines, challenges pertaining to correct cell geometry, as well
as sarcomeric and cardiac cell junction assembly and organization still hinder a wider adoption of
this powerful and refined model. Here we describe a novel platform formatted into high density (384
and 1536-well) screening plates that contains hiPSC-derived cardiomyocytes pre-plated in a
microstructure that emulates correct cardiac muscle fiber organization. Our platform leads to
improved sarcomeric organization, as seen by readily identifiable, correctly patterned myofibrils
along the cell body which tend to be absent, undefined or disarrayed when cardiomyocytes are
plated in standard cell cultureware. Plakogoblin, a key component of cardiac cell junctions, shows
correct targeting to distal intercalated discs in our platform, as opposed to an unrestricted, peripheric
localization to the cell membrane in standard cell cultureware. In our platform we also observe
increased gene expression of ryr2, atp2a2, and pln, key components of cardiomyocyte calcium
handling pathways, which are crucial for cardiac physiology. The expression levels of cardiac ion
channel genes such as cacnac1c, scn5a, kcne1, kcnq1 as well as cardiac cell junction components
gja1, gja5 and dsp are also increased.
Key Words: Human iPS cardiomyocytes physiological accuracy