Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Research Department, Rinaldi Fontani Foundation, Florence, Italy.
PLoS One. 2019 Jan 23;14(1):e0211188. doi: 10.1371/journal.pone.0211188. eCollection 2019.
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.
目前已知，通过调节特定的信号通路，可以在体外将多能干细胞诱导分化为心脏谱系细胞，但也众所周知，尽管目前可用的条件培养基显著增加了心肌细胞的产量，但由此产生的心脏发生仍然是一个高度可变的过程。先前的研究表明，通过 Radio Electric Asymmetric Conveyer（REAC）技术不对称传递的无线电波能够使 R1 胚胎干细胞和人脂肪来源干细胞向心脏表型分化。本研究旨在探讨 REAC 的物理刺激与特定化学诱导剂的组合是否能增强人诱导多能干细胞（iPSCs）的心脏发生潜能。在含有 BMP4 和 WNT 抑制剂的心脏发生培养基中培养的 iPSCs 出现心脏样表型，在最初的 72 小时内，仅在早期命运分化过程中进行 REAC 处理，就能显著增加。与仅在心脏发生培养基中培养的细胞相比，REAC 处理的 iPSCs 中特定的心脏发生转录物的表达上调，并且在搏动簇的数量上也表现出形态上的增加。我们的结果表明，REAC 提供的细胞动力学的物理调节为在心脏发生环境中模拟 iPSC 心脏样命运提供了一种经济有效的策略。
