Extracellular Nanomatrix-Induced Self-Organization of Neural Stem Cells into Miniature Substantia Nigra-Like Structures with Therapeutic Effects on Parkinsonian Rats

Zhang, Shiqing1,2,3; Sun, Peng4,5; Lin, Kaili1,2; Chan, Florence Hiu Ling6; Gao, Qi6; Lau, Wai Fung4; Roy, Vellaisamy A. L.7; Zhang, Hongqi8; Lai, King Wai Chiu6; Huang, Zhifeng2,3,4,9; Yung, Ken Kin Lam1,2,3,9

2019-09-30

10.1002/advs.201901822

ADVANCED SCIENCE   影响因子和分区

21983844

2198-3844

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.

extracellular nanomatrix neural stem cells Parkinson's disease specific neuronal subtype differentiation substantia nigra-like structures

SCI ; EI

英语

其他

HKRGC[CityU11205815] ; HKRGC[CityU11205514]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000488586300001

WILEY

20194407596009

Biocompatibility ; Cytology ; Diagnosis ; Electrophysiology ; Neurodegenerative diseases ; Rats ; Silica ; Stem cells

Bioengineering and Biology:461

Web of Science

1.Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Kowloon, Hong Kong, Peoples R China
2.HKBU, Golden Meditech Ctr NeuroRegenerat Sci, Kowloon Tong, Kowloon, Hong Kong, Peoples R China
3.HKBU Inst Res & Continuing Educ, 9F Ind Complex Shenzhen Virtual Univ Pk, Shenzhen 518057, Guangdong, Peoples R China
4.HKBU, Dept Phys, Kowloon Tong, Kowloon, Hong Kong, Peoples R China
5.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen 518000, Guangdong, Peoples R China
6.City Univ Hong Kong CityU, Dept Biomed Engn, Kowloon Tong, Kowloon, Chee Ave, Hong Kong, Peoples R China
7.City Univ Hong Kong, Dept Mat Sci & Engn, Kowloon Tong, Kowloon, Chee Ave, Hong Kong, Peoples R China
8.HKBU, Sch Chinese Med, Kowloon Tong, Kowloon, Hong Kong, Peoples R China
9.HKBU, Inst Adv Mat, State Key Lab Environm & Biol Anal, Kowloon Tong,Kowloon, Hong Kong, Peoples R China

Zhang, Shiqing,Sun, Peng,Lin, Kaili,et al. Extracellular Nanomatrix-Induced Self-Organization of Neural Stem Cells into Miniature Substantia Nigra-Like Structures with Therapeutic Effects on Parkinsonian Rats[J]. ADVANCED SCIENCE,2019,6(24).

Zhang, Shiqing.,Sun, Peng.,Lin, Kaili.,Chan, Florence Hiu Ling.,Gao, Qi.,...&Yung, Ken Kin Lam.(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).

Zhang, Shiqing,et al."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(2019).