1. Academic Validation
  2. Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling

Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling

  • Biomaterials. 2021 Jan;268:120585. doi: 10.1016/j.biomaterials.2020.120585.
Liumin He 1 Zhongqing Sun 2 Jianshuang Li 3 Rong Zhu 4 Ben Niu 2 Ka Long Tam 5 Qiao Xiao 6 Jun Li 6 Wenjun Wang 7 Chi Ying Tsui 5 Vincent Wing Hong Lee 2 Kwok-Fai So 8 Ying Xu 6 Seeram Ramakrishna 9 Qinghua Zhou 10 Kin Chiu 11
Affiliations

Affiliations

  • 1 Department of Spine Surgery, The 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, PR China; College of Life Science and Technology, Jinan University, Guangzhou, 510632, Guangdong, PR China. Electronic address: helm9@mail.sysu.edu.cn.
  • 2 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.
  • 3 Zhuhai Institute of Translational Medicine Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, PR China; The First Affiliated Hospital, The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, Guangdong, PR China.
  • 4 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; MOE Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, 510632, PR China.
  • 5 Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong SAR, PR China.
  • 6 MOE Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, 510632, PR China.
  • 7 The First Affiliated Hospital, The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, Guangdong, PR China.
  • 8 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; MOE Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, 510632, PR China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, PR China.
  • 9 MOE Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, 510632, PR China; Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117576, Singapore.
  • 10 Zhuhai Institute of Translational Medicine Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, PR China; The First Affiliated Hospital, The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, Guangdong, PR China. Electronic address: gene@email.jnu.edu.cn.
  • 11 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, PR China. Electronic address: datwai@hku.hk.
Abstract

Neural stem cells (NSCs) transplantation at the injury site of central nerve system (CNS) makes it possible for neuroregeneration. Long-term cell survival and low proliferation, differentiation, and migration rates of NSCs-graft have been the most challenging aspect on NSCs application. New multichannel electrical stimulation (ES) device was designed to enhance neural stem cells (NSCs) differentiation into mature neurons. Compared to controls, ES at nanoscale topography enhanced the expression of mature neuronal marker, growth of the neurites, concentration of BDNF and electrophysiological activity. RNA Sequencing analysis validated that ES promoted NSC-derived neuronal differentiation through enhancing Autophagy signaling. Emerging evidences showed that insufficient or excessive Autophagy contributes to neurite degeneration. Excessive ES current were able to enhance neuronal Autophagy, the neuronal cells showed poor viability, reduced neurite outgrowth and electrophysiological activity. Well-controlled Autophagy not only protects against neurodegeneration, but also regulates neurogenesis. Current NSC treatment protocol efficiently enhanced NSC differentiation, maturation and survival through combination of proper ES condition followed by balance of Autophagy level in the Cell Culture system. The successful rate of such protreated NSC at injured CNS site should be significantly improved after transplantation.

Keywords

Autophagy; Carbon nanotubes; Differentiation; Electrical stimulation; Neural stem cell.

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