posted on 2022-12-30, 18:36authored byAlejandra Patino-Guerrero, Ruben D. Ponce Wong, Vikram D. Kodibagkar, Wuqiang Zhu, Raymond Q. Migrino, Oliver Graudejus, Mehdi Nikkhah
The prevalence of cardiovascular
risk factors is expected
to increase
the occurrence of cardiovascular diseases (CVDs) worldwide. Cardiac
organoids are promising candidates for bridging the gap between in vitro experimentation and translational applications
in drug development and cardiac repair due to their attractive features.
Here we present the fabrication and characterization of isogenic scaffold-free
cardiac organoids derived from human induced pluripotent stem cells
(hiPSCs) formed under a supplement-deprivation regimen that allows
for metabolic synchronization and maturation of hiPSC-derived cardiac
cells. We propose the formation of coculture cardiac organoids that
include hiPSC-derived cardiomyocytes and hiPSC-derived cardiac fibroblasts
(hiPSC-CMs and hiPSC-CFs, respectively). The cardiac organoids were
characterized through extensive morphological assessment, evaluation
of cellular ultrastructures, and analysis of transcriptomic and electrophysiological
profiles. The morphology and transcriptomic profile of the organoids
were improved by coculture of hiPSC-CMs with hiPSC-CFs. Specifically,
upregulation of Ca2+ handling-related genes, such as RYR2
and SERCA, and structure-related genes, such as TNNT2 and MYH6, was
observed. Additionally, the electrophysiological characterization
of the organoids under supplement deprivation shows a trend for reduced
conduction velocity for coculture organoids. These studies help us
gain a better understanding of the role of other isogenic cells such
as hiPSC-CFs in the formation of mature cardiac organoids, along with
the introduction of exogenous chemical cues, such as supplement starvation.