Acoustically Accelerated Neural Differentiation of Human Embryonic Stem Cells

Chao Sun, Yinhua Dong, Jun Wei, Meng Cai, Dongfang Liang, Yongqing Fu, You Zhou, Yi Sui, Fangda Wu, Roman Mikhaylov, Hanlin Wang, Feifei Fan, Zhihua Xie, Mercedes Stringer Martin, Zhiyong Yang, Zhenlin Wu, Liangfei Tian, Xin Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Human embryonic stem cells (hESCs) and their derived products offer great promise for targeted therapies and drug screening, however, the hESC differentiation process of mature neurons is a lengthy process. To accelerate the neuron production, an acoustic stimulator producing surface acoustic waves (SAWs) is proposed and realized by clamping a flexible printed circuit board (PCB) directly onto a piezoelectric substrate. Neural differentiation of the hESCs is greatly accelerated after application of the acoustic stimulations. Acceleration mechanisms for neural differentiation have been explored by bulk RNA sequencing, quantitative polymerase chain reaction (qPCR) and immunostaining. The RNA sequencing results show changes of extracellular matrix-related and physiological activity-related gene expression in the low or medium SAW dose group and the high SAW dose group, respectively. The neural progenitor cell markers, including Pax6, Sox1, Sox2, Sox10 and Nkx2-1, are less expressed in the SAW dose groups compared with the control group by the qPCR. Other genes including Alk, Cenpf, Pcdh17, and Actn3 are also found to be regulated by the acoustic stimulation. Moreover, the immunostaining confirmed that more mature neuron marker Tuj1-positive cells, while less stem cell marker Sox2-positive cells, are presented in the SAW dose groups. These results indicate that the SAW stimulation accelerated neural differentiation process. The acoustic stimulator fabricated by using the PCB is a promising tool in regulation of stem cell differentiation process applied in cell therapy.
Original languageEnglish
JournalActa Biomaterialia
Early online date29 Jul 2022
DOIs
Publication statusE-pub ahead of print - 29 Jul 2022

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