Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration

Lin, Li; Lin, Hefeng; Bai, Shan; Zheng, Lianfang; Zhang, Xiaoming

doi:10.1016/j.neuint.2018.02.007

Cited by 79 publications

(55 citation statements)

References 38 publications

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“…The main treatment methods for SCI currently include drug therapy, surgical treatment, and transplantation therapy. These treatments aim to reduce secondary injury and promote nerve recovery and regeneration [3][4][5]. However, no SCI treatment can achieve a complete cure or exert significant curative effects in the clinic.…”

Section: Introductionmentioning

confidence: 99%

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKβ/NF-κB/A20 Pathway After Spinal Cord Injury

Deng

Gao

Cen

et al. 2018

Cell Physiol Biochem

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Background/Aims: miR-136-5p participates in recovery after spinal cord injury (SCI) via an unknown mechanism. We investigated the mechanism underlying the involvement of miR-136-5p in the inflammatory response in a rat model of SCI. Methods: Sprague-Dawley rat astrocytes were cultured in vitro to construct a reporter plasmid. Luciferase assays were used to detect the ability of miR-136-5p to target the IKKβ and A20 genes. Next, recombinant lentiviral vectors were constructed, which either overexpressed miR-136-5p or inhibited its expression. The influence of miR-136-5p overexpression and miR-136-5p silencing on inflammation was observed in vivo in an SCI rat model. The expression of IL-1β, IL-6, TNF-α, IFN-α, and related proteins (A20, IKKβ, and NF-κB) was detected. Results: In vitro studies showed that luciferase activity was significantly activated in the presence of the 3’ untranslated region (UTR) region of the IKKβ gene after stimulation of cells with miR-136-5p. However, luciferase activity was significantly inhibited in the presence of the 3’UTR region of the A20 gene. Thus, miR-136-5p may act directly on the 3’UTR regions of the IKKβ and A20 genes to regulate their expression. miR-136-5p overexpression promoted the production of related cytokines and NF-κB in SCI rats and inhibited the expression of A20 protein. Conclusion: Overexpression of miR-136-5p promotes the generation of IL-1β, IL-6, TNF-α, IFN-α, IKKβ, and NF-κB in SCI rats but inhibits the expression of A20. Under these conditions, inflammatory cell infiltration into the rat spinal cord increases and injury is significantly aggravated. Silencing of miR-136-5p significantly reduces the protein expression results described after miR-136-5p overexpression and ameliorates the inflammatory cell infiltration and damage to the spinal cord. Therefore, miR-136-5p might be a new target for the treatment of SCI.

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Section: Introductionmentioning

confidence: 99%

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKβ/NF-κB/A20 Pathway After Spinal Cord Injury

Deng

Gao

Cen

et al. 2018

Cell Physiol Biochem

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“…NSCs reduce neutrophils and M1 macrophages; down-regulate TNFα, IL-1 β, IL-6 and IL-12; improve functional recovery; and decrease apoptosis and microglial activation, thus improving locomotor and sensory functions [ 116 ]. BMSCs improve tissue protection and locomotor function, increase neurotropic growth factor, activate M2 macrophages and inhibit glial scar formation [ 117 ]. OECs reduce scar size and increase neurofilament sprouting and axon functions [ 118 ].…”

Section: Introductionmentioning

confidence: 99%

Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms

Anjum

Yazid

Daud

et al. 2020

IJMS

605

419

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Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.

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“…Bone mesenchymal stem cells (BMSCs) have low immunogenicity and potential ability to promote axonal outgrowth and differentiate into cells that express mature neuronal markers, and therefore, can be served as the seed cell for the engineering spinal cord [29,30]. However, there is still a prominent problem of low survival rate need to be solved [31]. It was reported that BMSCs disappeared from the spinal cord in 3-4 weeks after transplantation [32].…”

Section: Introductionmentioning

confidence: 99%

Histological and functional outcomes in a rat model of hemisected spinal cord with sustained VEGF/NT-3 release from tissue-engineered grafts

Zhang

Zhou

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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Microvascular disturbance, excessive inflammation and gliosis are key pathophysiologic changes in relation to functional status following the traumatic spinal cord injury (SCI). Continuous release of vascular endothelial growth factor (VEGF) to the lesion site was proved be able to promote the vascular remodelling, whereas the effects on reduction of inflammation and gliosis remain unclear. Currently, aiming at exploring the synergistic roles of VEGF and neurotrophin-3 (NT-3) on angiogenesis, anti-inflammation and neural repair, we developed a technique to co-deliver VEGF 165 and NT-3 locally with a homotopic graft of tissue-engineered acellular spinal cord scaffold (ASCS) in a hemisected (3 mm in length) SCI model. As the potential in secretion of growth factors (GFs), bone mesenchymal stem cells (BMSCs) were introduced with the aim to enhance the VEGF/NT-3 release. Our data demonstrate that sustained VEGF/NT-3 release from ASCS significantly increases the local levels of VEGF/NT-3 and angiogenesis, regardless of whether it is in combination with BMSCs transplantation that exhibits positive effects on anti-inflammation, axonal outgrowth and locomotor recovery. This study verifies that co-delivery of VEGF/NT-3 reduces inflammation and gliosis in the hemisected spinal cord, promotes axonal outgrowth and results in better locomotor recovery, while the BMSCs transplantation facilitates these functions limitedly.

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Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration

Cited by 79 publications

References 38 publications

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKβ/NF-κB/A20 Pathway After Spinal Cord Injury

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKβ/NF-κB/A20 Pathway After Spinal Cord Injury

Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms

Histological and functional outcomes in a rat model of hemisected spinal cord with sustained VEGF/NT-3 release from tissue-engineered grafts

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