scholarly journals IL-1β-induces NF-κB and upregulates microRNA-372 to inhibit spinal cord injury recovery

2017 ◽  
Vol 117 (6) ◽  
pp. 2282-2291 ◽  
Author(s):  
Wei Zhou ◽  
Tongzhou Yuan ◽  
Youshui Gao ◽  
Peipei Yin ◽  
Wei Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Functional Recovery ◽  
Neuronal Damage ◽  
Critical Role ◽  
Myeloperoxidase Activity ◽  
Cell Transplant ◽  
Tissue Water ◽  
Cord Injury

Excessive inflammation including IL-1β-initiated signaling is among the earlies reactions that can cause neuronal damage following spinal cord injury (SCI). It has been suggested that microRNAs may participate in stem cell repair to facilitate functional recovery following SCI. In this study we have shown that in cultured human neural stem cells (hNSC), IL-1β reduced the expression of both KIF3B (kinesin family member 3B) and NOSIP (nitric oxide synthase-interacting protein), two key modulators for restricting inflammation and promoting neuronal regeneration. The induction of microRNA-372 (miR-372) by IL-1β is specifically responsible for the inhibition of KIF3B and NOSIP. The 3′-untranslated regions (UTRs) of both KIF3B and NOSIP contain targeting sequences to miR-372 that directly inhibit their expression. Moreover, we found that the expression of miR-372 was stimulated in hNSC by IL-1β through an NF-κB binding site at its promoter region. Finally, stable overexpression of miR-372 inhibitor in hNSC rescued the IL-1β-induced impairment as shown by significant improvements in tissue water content, myeloperoxidase activity, and behavioral assessments in SCI rats. These findings suggest a critical role of miR-372 in inflammatory signaling and pinpoint a novel target for the treatment of acute SCI. NEW & NOTEWORTHY Our data demonstrate that IL-1β can impair the functional recovery of neural stem cell transplant therapy for spinal cord injury (SCI) treatment in rats. This effect is dependent on microRNA-372 (miR-372)-dependent gene repression of KIF3B and NOSIP. Therefore, specific knockdown of miR-372 may provide benefits for SCI treatments.

scholarly journals Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix Promotes Structural and Functional Recovery Following Spinal Cord Injury in Rats

2018 ◽  
Vol 9 ◽  
Author(s):  
Yana O. Mukhamedshina ◽  
Elvira R. Akhmetzyanova ◽  
Alexander A. Kostennikov ◽  
Elena Y. Zakirova ◽  
Luisa R. Galieva ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Functional Recovery ◽  
Fibrin Matrix ◽  
Cord Injury

scholarly journals Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

2020 ◽  
Author(s):  
Xu Yan ◽  
Yong Cao ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Umbilical Vein ◽  
Motor Evoked Potential ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Cord Injury

Abstract Background: Spinal cord injury (SCI) is a devastating clinical diseasewithout effectivetherapeuticapproach recently. In this study, we aim to investigate the effect of locally injection with exosome derived human urine stem cell (USC) embedding with hydrogelcould improve the spinal cord functional recovery after injury and the underlying mechanism.Methods:Exosome were isolate from USC andidentified by transmission electron microscopy and western blot. Functional assays using human umbilical vein endothelial cell (HUVEC) in vitro were performed to assess the effects of USC-Exosdeliverythe angiopoietin-like protein 3 (ANGPTL3) on tube formation and migration as well as their regulatory role in the PI3K/AKT signaling pathway activation. In vivo experiment we locally injection with exosome derived USC embedding with hydrogel for treatment of SCI. The effects of USC-Exos on functional recovery in spinal cord injury mice were tested by measuring motor evoked potential, histological and neovascular numbers. Meanwhile, the role of the candidate protein ANGPTL3 in USC-Exo for promoting angiogenesisin SCI was assessed.Results:In current study, we demonstrate that when given locallyinjection with exosomederivedhuman urine stem cell (USC) embeddingwith hydrogelcould pass the spinal cord blood brain barrier and delivery the angiopoietin-like protein 3 (ANGPTL3) to the injured spinal cord region. In addition, the administration of exosome derived from human USC could enhance spinal cord neurological functional recovery by promoting angiogenesis.The mechanism studies revealed that ANGPTL3 are enriched in USCexosome(USC-Exo) and required for USC exosome promoting angiogenesis. Functional studies further confirmed the effects caused by exosome derived from USC on angiogenesis wasmediated by PI3K/AKT signaling pathway. Conclusion:Collectively, our results indicated that USC derived exosome serve as a critical regulator of angiogenesis by transferring ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals Current progress of rehabilitative strategies in stem cell therapy for spinal cord injury: a review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Syoichi Tashiro ◽  
Osahiko Tsuji ◽  
Munehisa Shinozaki ◽  
Takahiro Shibata ◽  
Takashi Yoshida ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Functional Recovery ◽  
Synergistic Effects ◽  
Regenerative Therapy ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Functional Training ◽  
Cord Injury

AbstractStem cell-based regenerative therapy has opened an avenue for functional recovery of patients with spinal cord injury (SCI). Regenerative rehabilitation is attracting wide attention owing to its synergistic effects, feasibility, non-invasiveness, and diverse and systemic properties. In this review article, we summarize the features of rehabilitation, describe the mechanism of combinatorial treatment, and discuss regenerative rehabilitation in the context of SCI. Although conventional rehabilitative methods have commonly been implemented alone, especially in studies of acute-to-subacute SCI, the combinatorial effects of intensive and advanced methods, including various neurorehabilitative approaches, have also been reported. Separating the concept of combined rehabilitation from regenerative rehabilitation, we suggest that the main roles of regenerative rehabilitation can be categorized as conditioning/reconditioning, functional training, and physical exercise, all of which are indispensable for enhancing functional recovery achieved using stem cell therapies.

scholarly journals RARE-16. A CASE REPORT OF AUTOGRAFT OLFACTORY STEM CELL TRANSPLANT FOR SPINAL CORD INJURY DEVELOPING INTO A PERSISTENT SPINAL MASS

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi163-vi163
Author(s):  
Rodica Bernatowicz ◽  
Navin Sabharwal ◽  
Emily Bennett ◽  
Abdi Ghodsi ◽  
Andrew Healy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Case Report ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Cord Injury

scholarly journals Ethanol Extract of Chinese Propolis Facilitates Functional Recovery of Locomotor Activity after Spinal Cord Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Masaki Kasai ◽  
Hidefumi Fukumitsu ◽  
Hitomi Soumiya ◽  
Shoei Furukawa
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Locomotor Activity ◽  
Mrna Expression ◽  
Functional Recovery ◽  
Neuronal Damage ◽  
Ethanol Extract ◽  
Inos Mrna ◽  
Cord Injury ◽  
Chinese Propolis

An ethanol extract of Chinese propolis (EECP) was given intraperitoneally to rats suffering from hemitransection of half of their spinal cord (left side) at the level of the 10th thoracic vertebra to examine the effects of the EECP on the functional recovery of locomotor activity and expression of mRNAs of inducible nitric oxide (NO) synthase (iNOS) and neurotrophic factors in the injury site. Daily administration of EECP after the spinal cord injury ameliorated the locomotor function, which effect was accompanied by a reduced lesion size. Furthermore, the EECP suppressed iNOS gene expression, thus reducing NO generation, and also increased the expression level of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the lesion site, suggesting that the EECP reduced the inflammatory and apoptotic circumstances through attenuation of iNOS mRNA expression and facilitation of mRNA expression of neurotrophins in the injured spinal cord. These results suggest that Chinese propolis may become a promising tool for wide use in the nervous system for reducing the secondary neuronal damage following primary physical injury.

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.

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