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Enhanced cardiac differentiation of human CVD patient-specific iPS cells by applying unidirectional electrical pulses using aligned electroactive nanofibrous scaffolds.

Research paper by Leila L Mohammadi Amirabad, Mohammad M Massumi, Mehdi M Shamsara, Iman I Shabani, Afshin A Amari, Majid M Mossahebi Mohammadi, Simzar S Hosseinzadeh, Saeid S Vakilian, Sarah K SK Steinbach, Mohammad Reza MR Khorramizadeh, Masoud M Soleimani, Jalal J Barzin

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: ACS Applied Materials & Interfaces



Abstract

In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appears 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-iPS cells were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors and exposed to electrical impulses for 1 hour/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 PCR for cardiac-related transcription factors (NKX2.5, GATA-4, 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-iPS cells.