Acoustically Accelerated Neural Differentiation of Human Embryonic Stem Cells

Sun, Chao, Dong, Yinhua, Wei, Jun, Cai, Meng, Liang, Dongfang, Fu, Yong Qing, Zhou, You, Sui, Yi, Wu, Fangda, Mikhaylov, Roman, Wang, Hanlin, Fan, Feifei, Xie, Zhihua, Stringer, Mercedes, Yang, Zhiyong, Wu, Zhenlin, Tian, Liangfei and Yang, Xin (2022) Acoustically Accelerated Neural Differentiation of Human Embryonic Stem Cells. Acta Biomaterialia. ISSN 1742-7061 (In Press)

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Official URL: https://doi.org/10.1016/j.actbio.2022.07.041

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.

Item Type: Article
Additional Information: Funding information: This work was supported by the Natural Science Basic Research Program of Shaanxi Province [grant number 2020JQ-233]; the Engineering and Physical Sciences Research Council (EPSRC) [grant numbers EP/P002803/1 and EP/P018998/1]; Special Interest Group for Acoustofluidics from UK Fluids Network (EP/N032861/1), and the International Exchange Grants from Royal Society [grant numbers IEC/NSFC/170142, IEC/NSFC/201078], and EPSRC NetworkPlus in Digitalised Surface Manufacturing (EP/S036180/1).
Uncontrolled Keywords: Embryonic stem cell, surface acoustic wave, acoustofluidics, interdigital transducer, neural differentiation
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
F300 Physics
Department: Faculties > Engineering and Environment > Mathematics, Physics and Electrical Engineering
Depositing User: John Coen
Date Deposited: 01 Aug 2022 14:49
Last Modified: 01 Aug 2022 15:34
URI: http://nrl.northumbria.ac.uk/id/eprint/49667

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