scholarly journals Sustained delivery of neurotrophic factors to treat spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
pp. 494-511
Author(s):  
Aikeremujiang Muheremu ◽  
Li Shu ◽  
Jing Liang ◽  
Abudunaibi Aili ◽  
Kan Jiang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Neural Regeneration ◽  
Sustained Delivery ◽  
Neural Repair ◽  
Cord Injury ◽  
Psychological Harm

Abstract Acute spinal cord injury (SCI) is a devastating condition that results in tremendous physical and psychological harm and a series of socioeconomic problems. Although neurons in the spinal cord need neurotrophic factors for their survival and development to reestablish their connections with their original targets, endogenous neurotrophic factors are scarce and the sustainable delivery of exogeneous neurotrophic factors is challenging. The widely studied neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, ciliary neurotrophic factor, basic fibroblast growth factor, and glial cell-derived neurotrophic factor have a relatively short cycle that is not sufficient enough for functionally significant neural regeneration after SCI. In the past decades, scholars have tried a variety of cellular and viral vehicles as well as tissue engineering scaffolds to safely and sustainably deliver those necessary neurotrophic factors to the injury site, and achieved satisfactory neural repair and functional recovery on many occasions. Here, we review the neurotrophic factors that have been used in trials to treat SCI, and vehicles that were commonly used for their sustained delivery.

scholarly journals Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury

2019 ◽  
Vol 20 (23) ◽  
pp. 6078 ◽  
Author(s):  
Kentaro Yamane ◽  
Haruo Misawa ◽  
Tomoyuki Takigawa ◽  
Yoshihiro Ito ◽  
Toshifumi Ozaki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Stem Cell Differentiation ◽  
Neural Regeneration ◽  
Therapeutic Effects ◽  
Positive Effects ◽  
Cord Injury ◽  
Hepatocyte Growth

Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy.

scholarly journals Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents

2021 ◽  
Vol 22 (8) ◽  
pp. 4141
Author(s):  
Hye-Lan Lee ◽  
Chung-Eun Yeum ◽  
Hye-Yeong Lee ◽  
Jinsoo Oh ◽  
Jong-Tae Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Growth Factor ◽  
Peripheral Nerve ◽  
Neural Crest ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Cord Injury

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.

Localized and sustained release of brain-derived neurotrophic factor from injectable hydrogel/microparticle composites fosters spinal learning after spinal cord injury

2016 ◽  
Vol 4 (47) ◽  
pp. 7560-7571 ◽  
Author(s):  
Zin Z. Khaing ◽  
Nikunj K. Agrawal ◽  
James H. Park ◽  
Shangjing Xin ◽  
Glendon C. Plumton ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Sustained Release ◽  
Sustained Delivery ◽  
Mediated Learning ◽  
Injectable Hydrogel ◽  
Cord Injury ◽  
Spinal Learning ◽  
Hydrogel Microparticle

Injectable hydrogel allows for sustained delivery of growth factor resulting in spinal mediated learning after injury.

scholarly journals Glucocorticoid Regulation of Ependymal Glia and Regenerative Potential after Spinal Cord Injury

2018 ◽  
Author(s):  
Craig M. Nelson ◽  
Han Lee ◽  
Randall G. Krug ◽  
Aichurok Kamalova ◽  
Nicolas N. Madigan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Immune Cells ◽  
Therapeutic Benefit ◽  
Neural Regeneration ◽  
Clinical Implications ◽  
Spinal Cord Tissue ◽  
Neural Repair ◽  
Early Management ◽  
Cord Injury

SummaryFollowing injury, the mammalian spinal cord forms a glial scar and fails to regenerate. In contrast, spinal cord tissue of vertebrate fish regenerates and restores function. Cord transection in zebrafish (Danio rerio) initially causes paralysis and neural cell death, with subsequent ependymal glial proliferation, extension of bipolar glia across the lesion, and neurogenesis. Axons extending from spared and nascent neurons along trans-lesional glial bridges restore functional connectivity. Here we report that glucocorticoids directly target the regeneration supporting changes in ependymal glia to inhibit neural repair. This effect is independent of hematogenic immune cells or microglia. Furthermore, glucocorticoid receptor signaling in ependymal glia is inversely regulated in rat models of spinal cord injury compared to zebrafish. The blockade of neural regeneration by glucocorticoids via a direct effect on ependymal glia has important clinical implications concerning the putative therapeutic benefit of corticosteroids in early management of spinal cord injury.

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