Schwann cell plasticity after spinal cord injury shown by neural crest lineage tracing

Glia ◽  
2011 ◽  
Vol 59 (5) ◽  
pp. 771-784 ◽  
Author(s):  
Narihito Nagoshi ◽  
Shinsuke Shibata ◽  
Makoto Hamanoue ◽  
Yo Mabuchi ◽  
Yumi Matsuzaki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Schwann Cell ◽  
Neural Crest ◽  
Lineage Tracing ◽  
Cell Plasticity ◽  
Cord Injury

Cell therapy of combat related spinal cord injury with use of adult neural crest-derived multipotent stem cells

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S223 ◽  
Author(s):  
V Grytsyk ◽  
A Rodnichenko ◽  
O Gubar ◽  
O Rybachuk ◽  
A Zlatska ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Cell Therapy ◽  
Neural Crest ◽  
Multipotent Stem Cells ◽  
Cord Injury

scholarly journals Imaging characteristics of chronic spinal cord injury identified during screening for a cell transplantation clinical trial

2019 ◽  
Vol 46 (3) ◽  
pp. E8
Author(s):  
Joshua D. Burks ◽  
Katie L. Gant ◽  
James D. Guest ◽  
Aria G. Jamshidi ◽  
Efrem M. Cox ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Schwann Cell ◽  
Cell Transplantation ◽  
Lesion Length ◽  
Screening Criteria ◽  
Imaging Characteristics ◽  
Cord Injury ◽  
A Cell

OBJECTIVEIn cell transplantation trials for spinal cord injury (SCI), quantifiable imaging criteria that serve as inclusion criteria are important in trial design. The authors’ institutional experience has demonstrated an overall high rate of screen failures. The authors examined the causes for trial exclusion in a phase I, open-lab clinical trial examining the role of autologous Schwann cell intramedullary transplantation. Specifically, they reviewed the imaging characteristics in people with chronic SCI that excluded applicants from the trial, as this was a common cause of screening failures in their study.METHODSThe authors reviewed MRI records from 152 people with chronic (> 1 year) SCI who volunteered for intralesional Schwann cell transplantation but were deemed ineligible by prospectively defined criteria. Rostral-caudal injury lesion length was measured along the long axis of the spinal cord in the sagittal plane on T2-weighted MRI. Other lesion characteristics, specifically those pertaining to lesion cavity structure resulting in trial exclusion, were recorded.RESULTSImaging records from 152 potential participants with chronic SCI were reviewed, 42 with thoracic-level SCI and 110 with cervical-level SCI. Twenty-three individuals (55%) with thoracic SCI and 70 (64%) with cervical SCI were not enrolled in the trial based on imaging characteristics. For potential participants with thoracic injuries who did not meet the screening criteria for enrollment, the average rostral-caudal sagittal lesion length was 50 mm (SD 41 mm). In applicants with cervical injuries who did not meet the screening criteria for enrollment, the average sagittal lesion length was 34 mm (SD 21 mm).CONCLUSIONSWhile screening people with SCI for participation in a cell transplantation clinical trial, lesion length or volume can exclude potential subjects who appear appropriate candidates based on neurological eligibility criteria. In planning future cell-based therapy trials, the limitations incurred by lesion size should be considered early due to the screening burden and impact on candidate selection.

scholarly journals Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dayu Pan ◽  
Yongjin Li ◽  
Fuhan Yang ◽  
Zenghui Lv ◽  
Shibo Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Schwann Cell ◽  
Western Blot ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Cord Injury ◽  
Toll Like Receptor 2

Abstract Background Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood–brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. Methods A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and β-III-tublin, respectively. TLR2f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2−/−). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKβ inhibitor SC-514 was used to validate the involved signaling pathway. Results Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKβ inhibitor SC-514 was also used to validate this signaling pathway. Conclusion Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

scholarly journals Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Junhao Liu ◽  
Ruoyao Li ◽  
Zucheng Huang ◽  
Junyu Lin ◽  
Wei Ji ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Schwann Cell ◽  
Motor Function ◽  
Neural Tissue ◽  
Glial Scar ◽  
Vehicle Group ◽  
Spinal Cord Tissue ◽  
Cord Injury

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg–1⋅day–1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.

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