scholarly journals Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis

2021 ◽  
Vol 15 ◽  
Author(s):  
Lei Wang ◽  
Sujie Gu ◽  
Jinlu Gan ◽  
Yi Tian ◽  
Fangcheng Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Targeted Delivery ◽  
Neuroprotective Effect ◽  
Cord Injury ◽  
Lesion Core

Spinal cord injury (SCI) is a devastating event characterized by severe motor, sensory, and autonomic dysfunction. Currently, there is no effective treatment. Previous studies showed neural growth factor (NGF) administration was a potential treatment for SCI. However, its targeted delivery is still challenging. In this study, neural stem cells (NSCs) were genetically modified to overexpress NGF, and we evaluated its therapeutic value following SCI. Four weeks after transplantation, we observed that NGF-NSCs significantly enhanced the motor function of hindlimbs after SCI and alleviated histopathological damage at the lesion epicenter. Notably, the survival NGF-NSCs at lesion core maintained high levels of NGF. Further immunochemical assays demonstrated the graft of NGF-NSCs modulated the microenvironment around lesion core via reduction of oligodendrocyte loss, attenuation of astrocytosis and demyelination, preservation of neurons, and increasing expression of multiple growth factors. More importantly, NGF-NSCs seemed to crosstalk with and activate resident NSCs, and high levels of NGF activated TrkA, upregulated cAMP-response element binding protein (CREB) and microRNA-132 around the lesion center. Taken together, the transplantation of NGF-NSCs in the subacute stage of traumatic SCI can facilitate functional recovery by modulating the microenvironment and enhancing endogenous neurogenesis in rats. And its neuroprotective effect may be mediated by activating TrkA, up-regulation of CREB, and microRNA-132.

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.

scholarly journals Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qiuji Wu ◽  
Ziyue Xiang ◽  
Yibo Ying ◽  
Zhiyang Huang ◽  
Yurong Tu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Histochemical Staining ◽  
Adeno Associated Virus ◽  
Nerve Growth ◽  
Cord Injury

AbstractThe ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.

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.

scholarly journals Rapid and Efficient Differentiation of Rodent Neural Stem Cells into Oligodendrocyte Progenitor Cells

2019 ◽  
Vol 41 (1-2) ◽  
pp. 79-93 ◽  
Author(s):  
Shen Li ◽  
Jiao Zheng ◽  
Linlin Chai ◽  
Mengsi Lin ◽  
Ruocheng Zeng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Progenitor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Cord Injury

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.

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