Abstract
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.
Highlights
Stem cell-based therapy currently represents a promising approach for regenerative medicine, the translation of the in vitro studies into clinical applications is in part complicated by the difficulty in obtaining a high yield of differentiation within specific and homogenous stem cell-derived lineages that can provide their safety
In the field of regenerative medicine induced pluripotent stem cells (iPSCs) hold a high promise for future development, owing to its easy and wide-ranging opportunities for harvesting, and for the possibility of being generated even by non-integrating technologies[21], one of the main issues is to find a way to improve their differentiation in order to create a stable population for further applications
Our results showed that the use of physical stimulation by Radio Electric Asymmetric Conveyer (REAC) in combination with cardioinductive medium was able to increase the modulation of transcription factors genes GATA4, NKX2.5, T-Box protein 5 (TBX5), mainly involved in cardiac fate in the early three days of differentiation
Summary
Stem cell-based therapy currently represents a promising approach for regenerative medicine, the translation of the in vitro studies into clinical applications is in part complicated by the difficulty in obtaining a high yield of differentiation within specific and homogenous stem cell-derived lineages that can provide their safety. Since spontaneous cardiogenesis is a low-yield, variable process even in embryonic stem cells, the current observation that REAC technology with specific treatment protocols can promote the achievement of a cardiac phenotype in hUiPSCs unravels novelty within the methods in use to commit stem cells toward cardiac-like cells and opens new perspectives for future clinical applications
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