title: Exogenous treatment with eicosapentaenoic acid supports maturation of cardiomyocytes derived from embryonic stem cells.
abstract: Embryonic stem cells offer multiple advantages over adult stem cells in terms of achieving acceptable number of functional cardiomyocytes to be exploited in cell therapy. However, differentiation efficacy is still a major issue to be solved before moving to regenerative medicine. Although a vast number of chemical compounds have been tested on efficiency of cardiac differentiation, the effect of fish oil components, such as eicosapentaenoic acid (EPA) on developmental bioenergetics, and hence cardiac differentiation, remained unstudied. EPA has been reported to have several cardioprotective effects, but there is no study addressing its role in cardiac differentiation. After mesoderm induction of embryoid bodies (EBs) derived from mouse embryonic stem cells (mESCs) in hanging drops initiated by ascorbic acid, they were treated with various concentrations of EPA. Gene and protein expression and functional properties of cardiomyocytes derived from ESCs were evaluated following treatment with various concentrations of EPA. Exposure to low concentrations of EPA (10 μM) increased percentage of beating colonies and beating area. This treatment also resulted in up to 3 fold increase in expression of NKX2-5, MEF2C, MYH6, TNNT2 and CX43. FACS analysis confirmed gene expression analysis with increased percentage of MYH6 positive cells in EPA-treated group compared to the control group. In contrast, the expression of genes coding for cardiac differentiation, remained constant or even declined with higher concentrations of EPA. In conclusion, we have demonstrated that treatment of mESCs undergoing cardiac differentiation with low concentration, but not high concentration of EPA up-regulate transcription of genes associated with cardiac development.
authors: Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran; Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Parisa
authors: P
authors: Shabani
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Zaniar
authors: Z
authors: Ghazizadeh
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Sara
authors: S
authors: Pahlavan
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Shiva
authors: S
authors: Hashemizadeh
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Hossein
authors: H
authors: Baharvand
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: aghdami@royaninstitute.org.
authors: Nasser
authors: N
authors: Aghdami
authors: Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. Electronic address: doostimd@sina.tums.ac.ir.
authors: Mahmood
authors: M
authors: Doosti
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism
chemical_list: D015118:Eicosapentaenoic Acid
keywords: Cardiomyocytes; Eicosapentaenoic acid; Embryonic stem cells