title: Synthetic sulfonyl-hydrazone-1 positively regulates cardiomyogenic microRNA expression and cardiomyocyte differentiation of induced pluripotent stem cells.
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.
authors: Translational Cardiomyology, Stem Cell Institute, K.U.Leuven, Leuven, Belgium.
authors: Mattia
authors: M
authors: Quattrocelli
authors: Giacomo
authors: G
authors: Palazzolo
authors: Irene
authors: I
authors: Agnolin
authors: Sabata
authors: S
authors: Martino
authors: Marina
authors: M
authors: Bouché
authors: Luigi
authors: L
authors: Anastasia
authors: Maurilio
authors: M
authors: Sampaolesi
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
chemical_list: D000943:Antigens, Differentiation; D006835:Hydrazones; D007004:Hypoglycemic Agents; D035683:MicroRNAs; D013450:Sulfones; C069276:peroxovanadate; D014638:Vanadates; C505409:Casp3 protein, mouse; D053148:Caspase 3