scholarly journals The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury

2014 ◽  
Vol 3 (2) ◽  
pp. 141-146 ◽  
Author(s):  
TIANYI WANG ◽  
WENQI YUAN ◽  
YONG LIU ◽  
YANJUN ZHANG ◽  
ZHIJIE WANG ◽  
...  
Author(s):  
Yibo Ying ◽  
Yifan Zhang ◽  
Yurong Tu ◽  
Min Chen ◽  
Zhiyang Huang ◽  
...  

Reducing neuronal death after spinal cord injury (SCI) is considered to be an important strategy for the renovation of SCI. Studies have shown that, as an important regulator of the development and maintenance of neural structure, acidic fibroblast growth factor (aFGF) has the role of tissue protection and is considered to be an effective drug for the treatment of SCI. Neural stem cells (NSCs) are rendered with the remarkable characteristics to self-replace and differentiate into a variety of cells, so it is promising to be used in cell transplantation therapy. Based on the facts above, our main aim of this research is to explore the role of NSCs expressing aFGF meditated by five hypoxia-responsive elements (5HRE) in the treatment of SCI by constructing AAV–5HRE–aFGF–NSCs and transplanting it into the area of SCI. Our research results showed that AAV–5HRE–aFGF–NSCs can effectively restore the motor function of rats with SCI. This was accomplished by inhibiting the expression of caspase 12/caspase 3 pathway, EIF2α–CHOP pathway, and GRP78 protein to inhibit apoptosis.


2019 ◽  
Vol 41 (1-2) ◽  
pp. 79-93 ◽  
Author(s):  
Shen Li ◽  
Jiao Zheng ◽  
Linlin Chai ◽  
Mengsi Lin ◽  
Ruocheng Zeng ◽  
...  

Oligodendrocyte progenitor cells (OPCs) may have beneficial effects in cell replacement therapy of neurodegenerative disease owing to their unique capability to differentiate into myelinogenic oligodendrocytes (OLs) in response to extrinsic signals. Therefore, it is of significance to establish an effective differentiation methodology to generate highly pure OPCs and OLs from some easily accessible stem cell sources. To achieve this goal, in this study, we present a rapid and efficient protocol for oligodendroglial lineage differentiation from mouse neural stem cells (NSCs), rat NSCs, or mouse embryonic stem cell-derived neuroepithelial stem cells. In a defined culture medium containing Smoothened Agonist, basic fibroblast growth factor, and platelet-derived growth factor-AA, OPCs could be generated from the above stem cells over a time course of 4–6 days, achieving a cell purity as high as ∼90%. In particular, these derived OPCs showed high expandability and could further differentiate into myelin basic protein-positive OLs within 3 days or alternatively into glial fibrillary acidic protein-positive astrocytes within 7 days. Furthermore, transplantation of rodent NSC-derived OPCs into injured spinal cord indicated that it is a feasible strategy to treat spinal cord injury. Our results suggest a differentiation strategy for robust production of OPCs and OLs from rodent stem cells, which could provide an abundant OPC source for spinal cord injury.


Physiology ◽  
2008 ◽  
Vol 23 (5) ◽  
pp. 296-304 ◽  
Author(s):  
Franz-Josef Obermair ◽  
Aileen Schröter ◽  
Michaela Thallmair

Growing knowledge about the role of neural progenitor cells supports the hope that stem cell-based therapeutic approaches aimed at restoring function in the lesioned central nervous system can be established. Possible therapies for promoting recovery after spinal cord injury include stimulating the formation of neurons and glial cells by endogenous progenitor cells. This article reviews the current knowledge about the nature of adult progenitor cells in the intact and injured spinal cord and summarizes possibilities and limitations of cellular replacement strategies based on manipulations of endogenous spinal cord progenitor cells and their environment.


2021 ◽  
Author(s):  
Lu Ding ◽  
Weiwei Chu ◽  
Yu Xia ◽  
Tian Li ◽  
Ming Shi ◽  
...  

AbstractSpinal cord injury (SCI) is a devastating central nervous system (CNS) disease with no satisfying therapies available. Mobilizing endogenous neural stem cells (NSCs) to trigger intrinsic regeneration exhibits promising potentials for SCI repair. However, neurogenesis from endogenous NSCs is extremely restricted in the non-neurogenic spinal cord after SCI. Accumulation of protein aggregates has been shown to impede quiescent NSCs activation and the subsequent neurogenesis. Here, we found that ubiquitin c-terminal hydrolase l-1 (UCHL1), a deubiquitinating enzyme, functioned to regulate NSCs activation and neurogenesis by reducing protein aggregations through ubiquitin-proteasome pathway (UPP) in vitro. Upregulation of UCHL1 in spinal cord NSCs of rats with complete transection SCI efficiently enhanced NSCs proliferation and neurogenesis, leading to significantly improved functional outcomes. Based on protein microarray analysis of cerebrospinal fluid (CSF), our results revealed that A1 reactive astrocytes acted to restrict NSCs neurogenesis by negatively regulating UCHL1-depentdent protein aggregates removal via the C3/Nrf2 signaling. Indeed, blockade of A1 astrocytes using neutralizing antibodies after SCI also led to NSCs activation, increased neurogenesis and remarkably enhanced motor function recovery. This study not only revealed a novel mechanism regulating NSCs-medicated neurogenesis in the spinal cord, but also provided new molecular targets for neural repair strategies after SCI.Graphical AbstractHighlightsUCHL1 facilitates NSCs activation by clearing intracellular protein aggregates through ubiquitin-proteasome approachA1 reactive astrocytes result in down-regulation of UCHL1 to inhibit spinal NSCs activation by C3 after SCIOverexpression of UCHL1 or blockade of A1 astrocytes lead to NSCs activation and neurons formation to promote SCI repair via UCHL1-proteasome pathway


2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  

2018 ◽  
Vol 11 (6) ◽  
pp. 1433-1448 ◽  
Author(s):  
Satoshi Nori ◽  
Mohamad Khazaei ◽  
Christopher S. Ahuja ◽  
Kazuya Yokota ◽  
Jan-Eric Ahlfors ◽  
...  

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