scholarly journals Targeted Inhibition of STAT3 in Neural Stem Cells Promotes Neuronal Differentiation and Functional Recovery in Rats with Spinal Cord Injury

2020 ◽  
Author(s):  
Tingting Li ◽  
xiaoyang zhao ◽  
Jing Duan ◽  
Shangbin Cui ◽  
Kai Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Functional Recovery ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Control Shrna ◽  
Cord Injury

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.

Functional Recovery Following Spinal Cord Hemisection Mediated by a Unique Polymer Scaffold Seeded with Neural Stem Cells

2000 ◽  
Vol 662 ◽  
Author(s):  
Erin Lavik ◽  
Yang D. Teng ◽  
David Zurakowski ◽  
Xianlu Qu ◽  
Evan Snyder ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Axonal Guidance ◽  
General Character ◽  
Cord Injury ◽  
Scaffold Structure ◽  
Spinal Cord Hemisection

AbstractA dual scaffold structure made of biodegradable polymers and seeded with neural stem cells has been developed to address the issues of spinal cord injury including axonal severance and the loss of neurons and glia. The general design of the scaffold is derived the structure of the spinal cord with an outer section which mimics the white matter with long axial pores to provide axonal guidance and an inner section seeded with neural stem cells to address the issues of cell replacement and mimic the general character of the gray matter. The seeded scaffold leads to improved functional recovery as compared with the lesion control or cells alone following spinal cord injury.

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 ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Injury Repair ◽  
Cord Injury

scholarly journals Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52787 ◽  
Author(s):  
Yoshiomi Kobayashi ◽  
Yohei Okada ◽  
Go Itakura ◽  
Hiroki Iwai ◽  
Soraya Nishimura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Common Marmoset ◽  
Cord Injury ◽  
Human Ipsc

scholarly journals Therapeutic Effect of BDNF-Overexpressing Human Neural Stem Cells (F3.BDNF) in a Contusion Model of Spinal Cord Injury in Rats

2021 ◽  
Vol 22 (13) ◽  
pp. 6970
Author(s):  
Da-Jeong Chang ◽  
Hwi-Young Cho ◽  
Seyoung Hwang ◽  
Nayeon Lee ◽  
Chunggab Choi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Inflammatory Cells ◽  
Thoracic Spinal Cord ◽  
Human Neural Stem Cells ◽  
Neural Lineage ◽  
Cord Injury

The most common type of spinal cord injury is the contusion of the spinal cord, which causes progressive secondary tissue degeneration. In this study, we applied genetically modified human neural stem cells overexpressing BDNF (brain-derived neurotrophic factor) (F3.BDNF) to determine whether they can promote functional recovery in the spinal cord injury (SCI) model in rats. We transplanted F3.BDNF cells via intrathecal catheter delivery after a contusion of the thoracic spinal cord and found that they were migrated toward the injured spinal cord area by MR imaging. Transplanted F3.BDNF cells expressed neural lineage markers, such as NeuN, MBP, and GFAP and were functionally connected to the host neurons. The F3.BDNF-transplanted rats exhibited significantly improved locomotor functions compared with the sham group. This functional recovery was accompanied by an increased volume of spared myelination and decreased area of cystic cavity in the F3.BDNF group. We also observed that the F3.BDNF-transplanted rats showed reduced numbers of Iba1- and iNOS-positive inflammatory cells as well as GFAP-positive astrocytes. These results strongly suggest the transplantation of F3.BDNF cells can modulate inflammatory cells and glia activation and also improve the hyperalgesia following SCI.

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