Direct neuronal differentiation of neural stem cells for spinal cord injury repair

Stem Cells ◽  
2021 ◽  
Vol 39 (8) ◽  
pp. 1025-1032 ◽  
Author(s):  
Weiwei Xue ◽  
Caixia Fan ◽  
Bing Chen ◽  
Yannan Zhao ◽  
Zhifeng Xiao ◽  
...  
2016 ◽  
Vol 26 (32) ◽  
pp. 5835-5847 ◽  
Author(s):  
Xing Li ◽  
Sumei Liu ◽  
Yannan Zhao ◽  
Jiayin Li ◽  
Wenyong Ding ◽  
...  

2018 ◽  
Vol 6 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Xing Li ◽  
Jianwu Dai

Severe spinal cord injury (SCI) induces massive proliferation of spinal cord neural stem cells (NSCs), which are considered a promising cell source for therapeutic neural repair.


2021 ◽  
Author(s):  
Xiang Li ◽  
Lingli Long ◽  
Yue Hu ◽  
Wenwu Zhang ◽  
Fangling Zhong ◽  
...  

Abstract Background: Neural stem cells (NSCs) transplantation has been considered as a potential strategy to reconnect the neural circuit after spinal cord injury (SCI) but the therapeutic effect was still unsatisfied because of the poor inflammatory microenvironment. Previous study reported that neuroprotection and inflammatory immunomodulation were considered to be most important mechanism of NSCs transplantation. In addition, Wnt4 has been considered to be neurogenesis and anti-inflammatory so that it would be an essential assistant agent for NSCs transplantation.Results: We report the first piece of evidence to confirm the interaction between Wnt4-modified NSCs and macrophages using NSCs- macrophages co-cultured system. Wnt4-modified NSCs induce M2 polarization and inhibit M1 polarization of macrophages through suppress TLR4/NF-κB signal pathway; furthermore, M2 cells promote neuronal differentiation of NSCs through MAPK/JNK signal pathway. In vivo, transplantation of Wnt4-modified NSCs improve inflammatory microenvironment through induce M2 polarization and inhibit M1 polarization of macrophages to promote axonal regeneration and tissue repair.Conclusion: The current study indicated that transplantation of Wnt4-modified NSCs mediate M2 polarization of macrophages to promote spinal cord injury repair. Our novel findings would provide more insight of SCI and help with identification of novel treatment strategy.


2020 ◽  
Author(s):  
Tingting Li ◽  
xiaoyang zhao ◽  
Jing Duan ◽  
Shangbin Cui ◽  
Kai Zhu ◽  
...  

Abstract BackgroundSignal transducer and activator of transcription protein 3 (STAT3) is expressed in neural stem cells (NSCs), and some studies have shown that STAT3 is involved in regulating NSC differentiation. However, the possible molecular mechanism and the role of STAT3 in spinal cord injury (SCI) are unknown. Thus, in the present study, we identified possible molecular mechanisms by which STAT3 regulates NSC differentiation in vitro and investigated the potential therapeutic effect of transplanting STAT3-silenced NSCs in rat SCI models in vivo.MethodsIn vitro, NSCs were divided into the following three groups: control, control shRNA, and STAT3-shRNA lentivirus groups. NSCs in each treatment group were examined for neuronal differentiation via immunofluorescence, and Western blot analysis was used to investigate the possible molecular mechanisms. In vivo, the rats were divided into four groups that underwent laminectomy and complete spinal cord transection accompanied by transplantation of control-shRNA-treated or STAT3-shRNA-treated NSCs at the injured site. Spinal cord-evoked potentials and the Basso-Beattie-Bresnahan score were used to examine functional recovery after SCI. Axonal regeneration and tissue repair were assessed via retrograde tracing using Fluorogold, hematoxylin-eosin staining and immunofluorescence.ResultsKnockdown of STAT3 promoted neuronal differentiation in NSCs and mechanistic target of mammal rapamycin (mTOR) activation in vitro, and transplantation of STAT3-RNAi-treated NSCs enhanced rat functional recovery and tissue repair, as well as neuronal differentiation of the transplanted NSCs in vivo.ConclusionsWe have provided in vitro and in vivo evidence that STAT3 is a negative regulator of NSC neuronal differentiation. Transplantation of STAT3-inhibited NSCs appears to be a promising potential strategy for enhancing the benefit of NSC-mediated regenerative cell therapy for SCI.


2020 ◽  
Vol 8 (18) ◽  
pp. 5145-5156
Author(s):  
Yunlong Zou ◽  
Dezun Ma ◽  
He Shen ◽  
Yannan Zhao ◽  
Bai Xu ◽  
...  

Neural stem/progenitor cell (NSPC)-based spinal cord injury (SCI) therapy is expected to bridge the lesion site by transplanting exogenous NSPCs for replacement of lost cells.


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