Extracellular nanomatrix-induced self-organization of neural stem cells into miniature substantia nigra-like structures with therapeutic effects on Parkinsonian rats

Shiqing ZHANG, Peng SUN, Kaili LIN, Florence Hiu Ling CHAN, Qi GAO, Wai Fung LAU, Vellaisamy A. L. ROY, Hongqi ZHANG, King Wai Chiu LAI, Zhifeng HUANG, Kin Lam Ken YUNG

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18 Citations (Scopus)

Abstract

Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson's disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN-like structures (mini-SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self-organization of mini-SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self-organization of the mini-SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini-SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self-organization of region-specific and functional brain-like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD. Copyright © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Original languageEnglish
Article number1901822
JournalAdvanced Science
Volume6
Issue number24
Early online dateSept 2019
DOIs
Publication statusPublished - Dec 2019

Citation

Zhang, S., Sun, P., Lin, K., Chan, F. H. L., Gao, Q., Lau, W. F., Roy, V. A. L., Zhang, H., Lai, K. W. C., Huang, Z., & Yung, K. K. L. (2019). Extracellular nanomatrix-induced self-organization of neural stem cells into miniature substantia nigra-like structures with therapeutic effects on Parkinsonian rats. Advanced Science, 6(24), Article 1901822. https://doi.org/10.1002/advs.201901822

Keywords

  • Extracellular nanomatrix
  • Neural stem cells
  • Parkinson's disease
  • Specific neuronal subtype differentiation
  • Substantia nigra-like structures

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