Characterization of a small molecule that promotes cell cycle activation of human induced pluripotent stem cell-derived cardiomyocytes.
Animals
Cell Cycle
/ drug effects
Cell Differentiation
/ drug effects
Cell Division
/ drug effects
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Gene Expression Regulation, Developmental
/ drug effects
Humans
Induced Pluripotent Stem Cells
/ drug effects
Mice
Myocardium
/ metabolism
Myocytes, Cardiac
/ drug effects
Regeneration
/ drug effects
Small Molecule Libraries
/ pharmacology
Cell cycle activation
Hippo pathway
Induced pluripotent stem cell-derived cardiomyocyte
Regeneration
Regenerative medicine
Small molecule
Journal
Journal of molecular and cellular cardiology
ISSN: 1095-8584
Titre abrégé: J Mol Cell Cardiol
Pays: England
ID NLM: 0262322
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
18
09
2018
revised:
18
01
2019
accepted:
23
01
2019
pubmed:
27
1
2019
medline:
19
6
2020
entrez:
27
1
2019
Statut:
ppublish
Résumé
Since regenerative capacity of adult mammalian myocardium is limited, activation of the endogenous proliferative capacity of existing cardiomyocytes is a potential therapeutic strategy for treating heart diseases accompanied by cardiomyocyte loss. Recently, we performed a compound screening and developed a new drug named TT-10 (C To test whether TT-10 can also promote the proliferative capacity of human cardiomyocytes, we investigated the efficacy of TT-10 on human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSCMs). The hiPSCs were established from monocytes obtained from healthy donors and cardiac differentiation was performed using a chemically defined protocol. As was observed in murine cardiomyocytes, TT-10 markedly promoted cell cycle activation and increased cell division of hiPSCMs. We then evaluated other effects of TT-10 on the functional properties of hiPSCMs by gene expression and cell motion analyses. We observed that TT-10 had no unfavorable effects on the expression of functional and structural genes or the contractile properties of hiPSCMs. Our results suggest that the novel drug TT-10 effectively activated the cell cycle of hiPSCMs without apparent functional impairment of myocardium, suggesting the potential of clinical usefulness of this drug.
Sections du résumé
BACKGROUND
Since regenerative capacity of adult mammalian myocardium is limited, activation of the endogenous proliferative capacity of existing cardiomyocytes is a potential therapeutic strategy for treating heart diseases accompanied by cardiomyocyte loss. Recently, we performed a compound screening and developed a new drug named TT-10 (C
METHODS AND RESULTS
To test whether TT-10 can also promote the proliferative capacity of human cardiomyocytes, we investigated the efficacy of TT-10 on human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSCMs). The hiPSCs were established from monocytes obtained from healthy donors and cardiac differentiation was performed using a chemically defined protocol. As was observed in murine cardiomyocytes, TT-10 markedly promoted cell cycle activation and increased cell division of hiPSCMs. We then evaluated other effects of TT-10 on the functional properties of hiPSCMs by gene expression and cell motion analyses. We observed that TT-10 had no unfavorable effects on the expression of functional and structural genes or the contractile properties of hiPSCMs.
CONCLUSIONS
Our results suggest that the novel drug TT-10 effectively activated the cell cycle of hiPSCMs without apparent functional impairment of myocardium, suggesting the potential of clinical usefulness of this drug.
Identifiants
pubmed: 30684499
pii: S0022-2828(18)30937-4
doi: 10.1016/j.yjmcc.2019.01.020
pii:
doi:
Substances chimiques
Small Molecule Libraries
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
90-95Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.