Synthetic sulfonyl-hydrazone-1 positively regulates cardiomyogenic microRNA expression and cardiomyocyte differentiation of induced pluripotent stem cells

Mattia Quattrocelli, Giacomo Palazzolo, Irene Agnolin, Sabata Martino, Marina Bouché, Luigi Anastasia, Maurilio Sampaolesi

Research output: Contribution to journalArticle

Abstract

Induced pluripotent stem cells (iPSCs) are obtained from adult cells through overexpression of pluripotency factors. iPSCs share many features with embryonic stem cells (ESCs), circumventing ethical issues, and, noteworthy, match donor's genotype. iPSCs represent therefore a valuable tool for regenerative medicine. Cardiac differentiation of ESCs can be enhanced via microRNAs (miRNAs) and small chemical compounds, which probably act as chromatin remodelers. Cardiomyogenic potential of iPSCs is currently intensely investigated for cell therapy or in vitro drug screening and disease modeling. However, influences of small compounds on iPSC-related cardiomyogenesis have not yet been investigated in details. Here, we compared the effects of two small molecules, bis-peroxo-vanadium (bpV) and sulfonyl-hydrazone-1 (SHZ) at varying concentrations, during cardiac differentiation of murine iPSCs. SHZ (5 μM) enhanced specific marker expression and cardiomyocyte yield, without loss of cell viability. In contrast, bpV showed negligible effects on cardiac differentiation rate and appeared to induce Casp3-dependent apoptosis in differentiating iPSCs. Furthermore, SHZ-treated iPSCs were able to increase beating foci rate and upregulate early and late cardiomyogenic miRNA expression (miR-1, miR-133a, and miR-208a). Thus, our results demonstrate that small chemical compounds, such as SHZ, can constitute a novel and clinically feasible strategy to improve iPSC-derived cardiac differentiation.

Original languageEnglish
Pages (from-to)2006-2014
Number of pages9
JournalJournal of Cellular Biochemistry
Volume112
Issue number8
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Bis-peroxo-vananadium
  • Cardiomyocytes
  • iPSCs
  • microRNAs
  • Sulfonyl-hydrazone

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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