title: Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds.
abstract: In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (β) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds. We established cardiovascular disease-specific induced pluripotent stem cells (CVD-iPSCs) from the fibroblasts of patients undergoing cardiothoracic surgeries. The CVD-iPSCs were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors, and exposed to electrical impulses for 1 h/day, over a 15-day time period in the bioreactor. The application of the unidirectional electrical stimulation to the cells significantly increased the number of cardiac Troponin T (cTnT+) cells in comparison to multidirectional electrical stimulation using random fibrous scaffolds. This was confirmed by real-time polymerase chain reaction for cardiac-related transcription factors (NKX2.5, GATA4, and NPPA) and a cardiac-specific structural gene (TNNT2). Here we report for the first time that applying electrical pulses in a unidirectional manner mimicking the unidirectional wave of electrical stimulation in the heart, could increase the derivation of cardiomyocytes from CVD-iPSCs.
authors.affiliation: Stem Cells Department, National Institute of Genetic Engineering and Biotechnology , Tehran, Iran.|School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran.
authors.forename: Leila
authors.identifier: http://orcid.org/0000-0003-1835-4563
authors.initials: L
authors.lastname: Mohammadi Amirabad
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario M5T 3H7, Canada.|Department of Physiology, University of Toronto , Toronto, Ontario M5S 1A8, Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Massumi
authors.affiliation: Stem Cells Department, National Institute of Genetic Engineering and Biotechnology , Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shamsara
authors.affiliation: Biomedical Engineering Department, Amirkabir University of Technology , Tehran, Iran.
authors.forename: Iman
authors.initials: I
authors.lastname: Shabani
authors.affiliation: Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz 61357-15794, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Amari
authors.affiliation: Stem Cells Biology Department, Stem Cell Technology Research Center , Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Mossahebi Mohammadi
authors.affiliation: School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran.
authors.forename: Simzar
authors.initials: S
authors.lastname: Hosseinzadeh
authors.affiliation: Stem Cells Biology Department, Stem Cell Technology Research Center , Tehran, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Vakilian
authors.affiliation: McEwen Centre for Regenerative Medicine, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Steinbach
authors.affiliation: Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences , Tehran, Iran.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Khorramizadeh
authors.affiliation: Stem Cells Biology Department, Stem Cell Technology Research Center , Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Biomaterials Department, Iran Polymer and Petrochemical Institute , Tehran, Iran.
authors.forename: Jalal
authors.identifier: http://orcid.org/0000-0002-4860-5805
authors.initials: J
authors.lastname: Barzin
mesh_terms: D002318:Cardiovascular Diseases; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D032383:Myocytes, Cardiac; D057139:Nanofibers; D054457:Tissue Scaffolds
keywords: PANI/PES fibrous scaffolds; cardiogenesis; cardiomyocytes; electrical impulse; iPSCs