Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo.

Scientific Reports
Hajime IchimuraYuji Shiba

Abstract

Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect "heart regeneration", replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transpla...Continue Reading

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Citations

Oct 23, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Yuji Shiba
Nov 17, 2020·Frontiers in Bioengineering and Biotechnology·Philippe Menasché
Jun 1, 2021·Seminars in Cell & Developmental Biology·M Juliana Gomez-GarciaMichael A Laflamme

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Methods Mentioned

BETA
flow cytometry
RNA-Seq

Software Mentioned

PCAtools
ImageJ
featureCounts
STAR
Trimmomatic
Xenome
clusterProfiler
edgeR

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