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PLoS One. 2019 Jan 23;14(1):e0211188. doi: 10.1371/journal.pone.0211188. eCollection 2019.

Physical stimulation by REAC and BMP4/WNT-1 inhibitor synergistically enhance cardiogenic commitment in iPSCs.

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Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Research Department, Rinaldi Fontani Foundation, Florence, Italy.
Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
National Laboratory of Molecular Biology and Stem Cell Engineering - National Institute of Biostructures and Biosystems-Eldor Lab, at Innovation Accelerators, CNR, Bologna, Italy.
Department of Regenerative Medicine, Rinaldi Fontani Institute, Florence, Italy.
IRF Shanghai Medical Sciences, Shanghai, China.
Evercyte GmbH, Vienna, Austria.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Center for developmental biology and reprogramming - CEDEBIOR, Department of Biomedical Sciences, University of Sassari and National Institute of Biostructures and Biosystems, Sassari, Italy.


It is currently known that pluripotent stem cells can be committed in vitro to the cardiac lineage by the modulation of specific signaling pathways, but it is also well known that, despite the significant increase in cardiomyocyte yield provided by the currently available conditioned media, the resulting cardiogenic commitment remains a highly variable process. Previous studies provided evidence that radio electric fields asymmetrically conveyed through the Radio Electric Asymmetric Conveyer (REAC) technology are able to commit R1 embryonic stem cells and human adipose derived stem cells toward a cardiac phenotype. The present study aimed at investigating whether the effect of physical stimulation by REAC in combination with specific chemical inductors enhance the cardiogenic potential in human induced pluripotent stem cells (iPSCs). The appearance of a cardiac-like phenotype in iPSCs cultured in the presence of a cardiogenic medium, based upon BMP4 and a WNT-inhibitor, was consistently increased by REAC treatment used only during the early fate differentiation for the first 72 hours. REAC-exposed iPSCs exhibited an upregulation in the expression of specific cardiogenic transcripts and morphologically in the number of beating clusters, as compared to cells cultured in the cardiogenic medium alone. Our results indicate that physical modulation of cellular dynamics provided by the REAC offers an affordable strategy to mimic iPSC cardiac-like fates in the presence of a cardiogenic milieu.

Conflict of interest statement

SR and VF are the inventors of the REAC technology. M.W. and A.S. are employed by Evercyte GmbH, Vienna, and S.R. and V.F. are partners in IRF Shanghai Medical Sciences. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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