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Aortic valve calcification is induced by the loss of ALDH1A1 and can be prevented by agonists of retinoic acid receptor alpha: preclinical evidence for drug repositioning

ABSTRACT: Study the effect of Am80 on osteoblast differentiation

ORGANISM(S): Homo sapiens

PROVIDER: GSE285688 | GEO | 2025/12/24

REPOSITORIES: GEO

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Aortic valve calcification is induced by the loss of ALDH1A1 and can be prevented by agonists of retinoic acid receptor alpha: preclinical evidence for drug repositioning, 2

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Am80 activates cardiomyocytes cell cycle via retinoic acid receptor for efficient transplantation

Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-cardiomyocytes) are promising sources for the regenerative therapy to treat heart failure. To realize this therapy, the engraftment potential of hiPSC-cardiomyocytes following the injection into the host heart should be improved. Here, we established the efficient method to analyze the cell cycle activity of hiPSC-cardiomyocytes using Fluorescence Ubiquitination-based Cell Cycle Indicator (FUCCI) system. High-throughput screening analysis using FUCCI-expressing hiPSC-cardiomyocytes identified a retinoic acid receptor (RAR) agonist, Am80, as an effective cell cycle activator in hiPSC-cardiomyocytes. The transplantation of hiPSC-cardiomyocytes treated by Am80 prior to the injection significantly enhanced the engraftment into the damaged mouse heart for 6 months. RNA sequencing analysis in Am80-treated iPSC-cardiomyocytes revealed that both RARA and RARB played important roles in the Am80-mediated cell cycle activation in hiPSC-cardiomyocytes. Collectively, this study highlights the effectiveness of FUCCI system to easily analyze the cell cycle status in hiPSC-cardiomyocytes and the cell cycle activation by Am80 is the possible strategy to increase the graft size following the cell transplantation into the damaged heart.

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