Scar tissue removal-activated endogenous neural stem cells aid Taxol-modified collagen scaffolds in repairing chronic long-distance transected spinal cord injury

2021 ◽  
Author(s):  
Wen Yin ◽  
Weiwei Xue ◽  
Hecheng Zhu ◽  
He Shen ◽  
Zhifeng Xiao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Scar Tissue ◽  
Collagen Scaffolds ◽  
Long Distance ◽  
Tissue Removal ◽  
Cord Injury ◽  
Endogenous Neural Stem Cells ◽  
Time Point

Only the first scar tissue removal is a key time point for chronic complete SCI repair. Endogenous NSCs could be intensively activated after the first scar tissue removal and contribute to the chronic SCI repair after bio-scaffold implantation.

Bridging the gap with functional collagen scaffolds: tuning endogenous neural stem cells for severe spinal cord injury repair

2018 ◽  
Vol 6 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Xing Li ◽  
Jianwu Dai
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Collagen Scaffolds ◽  
Neural Repair ◽  
Injury Repair ◽  
Cord Injury ◽  
Cell Source ◽  
Endogenous Neural Stem Cells

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.

scholarly journals Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells after Spinal Cord Injury

Neuron ◽  
2014 ◽  
Vol 83 (4) ◽  
pp. 789-796 ◽  
Author(s):  
Paul Lu ◽  
Grace Woodruff ◽  
Yaozhi Wang ◽  
Lori Graham ◽  
Matt Hunt ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Axonal Growth ◽  
Long Distance ◽  
Cord Injury ◽  
Induced Pluripotent

scholarly journals GP.04 Smart human neural stem cells to degrade scar and optimize regeneration after traumatic cervical spinal cord injury

2018 ◽  
Vol 45 (s2) ◽  
pp. S9-S9
Author(s):  
CS Ahuja ◽  
M Khazaei ◽  
P Chan ◽  
J Bhavsar ◽  
Y Yao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Chronic Injury ◽  
Long Distance ◽  
Degrading Enzyme ◽  
Genetically Engineer ◽  
Cord Injury

Background: Human induced pluripotent stem cell-derived neural stem cells (hiPS-NSCs) represent an exciting therapeutic approach for traumatically spinal cord injury (SCI). Unfortunately, most patients are the in chronic injury phase where a dense perilesional chondroitin sulfate proteoglycan (CSPG) scar significantly hinders regeneration. CSPG-degrading enzymes can enhance NSC-mediated recovery, however, nonspecific intrathecal administration causes off-target effects. We aimed to genetically engineer hiPS-NSCs to express a scar-degrading ENZYME into their local environment to enhance functional recovery. Methods: A bicistronic scar-degrading ENZYME and RFP reporter vector was non-virally integrated into hiPS-NSCs and monoclonalized. ENZYME activity was assessed by WST-1 and DMMB biochemical assays and an in vitro CSPG spot assay with hiPS-NSC-derived neurons. To assess in vivo efficacy, T-cell deficient rats (N=60) with chronic (8wk) C6-7 SCIs were randomized to receive (1)SMaRT cells, (2)hiPS-NSCs, (3)vehicle, or (4)sham surgery. Results: SMaRT cells retained key hiPS-NSC characteristics while stably expressing ENZYME. The expressed ENZYME could appropriately degrade in vitro and ex vivo CSPGs. While blinded neurobehavioural and immunohistochemical assessments are ongoing at 40wks post-injury, an interim analysis demonstrated human cells extending remarkably long (≥20,000µm) axons along host white matter tracts. Conclusions: This work provides exciting proof-of-concept data that genetically-engineered SMaRT cells can degrade CSPGs and human NSCs can extend long-distance processes in chronic SCI.

scholarly journals Methylprednisolone inhibits the proliferation of endogenous neural stem cells in nonhuman primates with spinal cord injury

2018 ◽  
Vol 29 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Jichao Ye ◽  
Yi Qin ◽  
Yong Tang ◽  
Mengjun Ma ◽  
Peng Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Nonhuman Primates ◽  
Therapy Group ◽  
Central Canal ◽  
Ependymal Cells ◽  
Control Group ◽  
Cord Injury ◽  
Endogenous Neural Stem Cells

OBJECTIVEThe aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (ENSCs) in nonhuman primates with spinal cord injury (SCI).METHODSA total of 14 healthy cynomolgus monkeys (Macaca fascicularis) (4–5 years of age) were randomly divided into 3 groups: the control group (n = 6), SCI group (n = 6), and methylprednisolone therapy group (n = 2). Only laminectomy was performed in the control animals at T-10. SCI was induced in monkeys using Allen’s weight-drop method (50 mm × 50 g) to injure the posterior portion of the spinal cord at T-10. In the methylprednisolone therapy group, monkeys were intravenously infused with methylprednisolone (30 mg/kg) immediately after SCI. All animals were intravenously infused with 5-bromo-2-deoxyuridine (BrdU) (50 mg/kg/day) for 3 days prior to study end point. The small intestine was dissected for immunohistochemical examination. After 3, 7, and 14 days, the spinal cord segments of the control and SCI groups were dissected to prepare frozen and paraffin sections. The proliferation of ENSCs was evaluated using BrdU and nestin immunofluorescence staining.RESULTSHistological examination showed that a larger number of mucosa epithelial cells in the small intestine of all groups were BrdU positive. Nestin-positive ependymal cells are increased around the central canal after SCI. After 3, 7, and 14 days of SCI, BrdU-positive ependymal cells in the SCI group were significantly increased compared with the control group, and the percentage of BrdU-positive cells in the left/right ventral horns and dorsal horn was significantly higher than that of the control group. Seven days after SCI, the percentages of both BrdU-positive ependymal cells around the central canal and BrdU– and nestin–double positive cells in the left/right ventral horns and dorsal horn were significantly lower in the methylprednisolone therapy group than in the SCI group.CONCLUSIONSWhile ENSCs proliferate significantly after SCI in nonhuman primates, methylprednisolone can inhibit the proliferation of ependymal cells after SCI.

scholarly journals Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury

Cell ◽  
2012 ◽  
Vol 150 (6) ◽  
pp. 1264-1273 ◽  
Author(s):  
Paul Lu ◽  
Yaozhi Wang ◽  
Lori Graham ◽  
Karla McHale ◽  
Mingyong Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Long Distance ◽  
Cord Injury

Training Neural Stem Cells on Functional Collagen Scaffolds for Severe Spinal Cord Injury Repair

2016 ◽  
Vol 26 (32) ◽  
pp. 5835-5847 ◽  
Author(s):  
Xing Li ◽  
Sumei Liu ◽  
Yannan Zhao ◽  
Jiayin Li ◽  
Wenyong Ding ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Collagen Scaffolds ◽  
Injury Repair ◽  
Cord Injury
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