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Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds Publisher Pubmed



Mohammadi Amirabad L1, 2 ; Massumi M3, 4 ; Shamsara M1 ; Shabani I5 ; Amari A6 ; Mossahebi Mohammadi M7 ; Hosseinzadeh S2 ; Vakilian S7 ; Steinbach SK8 ; Khorramizadeh MR9 ; Soleimani M7 ; Barzin J10
Authors
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Authors Affiliations
  1. 1. Stem Cells Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  2. 2. School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, M5T 3H7, ON, Canada
  4. 4. Department of Physiology, University of Toronto, Toronto, M5S 1A8, ON, Canada
  5. 5. Biomedical Engineering Department, Amirkabir University of Technology, Tehran, Iran
  6. 6. Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 61357-15794, Iran
  7. 7. Stem Cells Biology Department, Stem Cell Technology Research Center, Tehran, Iran
  8. 8. McEwen Centre for Regenerative Medicine, Toronto, M5G 1L7, ON, Canada
  9. 9. Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran

Source: ACS Applied Materials and Interfaces Published:2017


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. © 2017 American Chemical Society.
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