Targeted Inhibition of Leucine-Rich Repeat and Immunoglobulin Domain-Containing Protein 1 in Transplanted Neural Stem Cells Promotes Neuronal Differentiation and Functional Recovery in Rats Subjected to Spinal Cord Injury*

Chen, Ningning; Cen, Jing Sheng; Wang, Jingnan; Qin, Gangjian; Long, Lingli; Wang, Le; Wei, Fuxin; Xiang, Qingfeng; Deng, David Y.B.; Wan, Yong

doi:10.1097/ccm.0000000000001351

Cited by 35 publications

(48 citation statements)

References 41 publications

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“…The role of the Notch signal pathway in SCI has attracted increasing attention (21). The Notch signal pathway renders the differentiation of spinal cord-derived stem cells into nerve cells, and inhibits that of neural stem cells into neurogliocytes, which contributes to the therapy for SCI (22). Notch signaling serves an important role in the development of the central nervous system, and Notch is essential for the directional differentiation and maintenance of the neural precursor cells (23).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury

et al. 2018

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The aim of the present study was to investigate whether microRNA‑381 is a potential therapeutic target for spinal cord injury (SCI) and its possible mechanism. Reverse transcription quantitative polymerase chain reaction (qPCR) for mRNA expression was used to analyze the changes of microRNA-381 expression. Cell viability and cell apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and ﬂow cytometry. Caspase‑3 activity was measured using caspase‑3 activity kit, and western blot analysis was used to measure the protein expression of neurogenic locus notch homolog protein 1 (Notch1), notch 1 intracellular domain (NICD) and transcription factor HES-1 (Hes1). The data showed that microRNA‑381 expression of model SCI rats was downregulated compared with that of control rats. Overexpression of microRNA‑381 promoted cell proliferation, and inhibited apoptosis and caspase‑3 and apoptosis regulator BAX (Bax) protein expression in neurocytes. Overexpression of microRNA‑381 also increased Wnt and β‑catenin protein expression, and suppressed the protein expression of Notch1, NICD and Hes1 in neurocytes. Wnt inhibitor, Wnt‑C59 (1 µmol/l), inhibited cell proliferation, promoted apoptosis and caspase‑3 and Bax protein expression, suppressed β‑catenin protein expression and induced Hes1 protein expression in neurocytes following microRNA‑381 overexpression. Notch inhibitor, FLI‑06 (1 µmol/l), promoted cell proliferation, inhibited apoptosis and caspase‑3 and Bax protein expression, and suppressed NICD and Hes1 protein expression in neurocytes following microRNA‑381 overexpression. Thus, this study showed that overexpression of microRNA‑381 promotes cell proliferation of neurocytes in SCI via Hes1 expression, which may be a novel important mechanism for SCI in clinical applications.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury

et al. 2018

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“…21,22 Briefly, the brain tissue was mechanically dissected and dissociated in Hanks Balanced Salt Solution, and the cell suspension was centrifuged at 1000 rpm for 5 minutes. Neural Stem Cell cultures were obtained from the fetal brains of embryonic day 14 rats, which were extracted from pregnant Sprague-Dawley (SD) rats (Laboratory Animal Center of Sun Yat-sen University, Guangzhou, China) and identify as previously described.…”

Section: Nsc Isolation and Culturingmentioning

confidence: 99%

Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury

Peng

Long

et al. 2019

FASEB j.

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Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, yet there are no effective therapies currently due to the failure of reconstructing the interruption of the neuroanatomical circuit. While neural stem cell (NSC) transplantation has been considered a potential strategy to repair the neural circuit after SCI, the efficacy of this strategy remains unproven. The main reason is that most of the transplanted NSC differentiates into astrocyte rather than neuron in the microenvironment of SCI. Our results demonstrated that Wnt4 significantly promotes the differentiation of NSC into neuron by activating both β‐catenin and MAPK/JNK pathways and suppressing the activation of Notch signaling, which is acknowledged as prevention of NSC differentiation into neuron, through downregulating NICD expression, translocating and preventing the combination of NICD and RbpJ in nucleus. In addition, Wnt4 rescues the negative effect of Jagged, the ligand of Notch signaling, to promote neuronal differentiation. Moreover, in vivo study, transplantation of Wnt4‐modified NSC efficaciously repairs the injured spinal cord and recovers the motor function of hind limbs after SCI. This study sheds new light into mechanisms that Wnt4‐modified NSC transplantation is sufficient to repair the injured spinal cord and recover the motor dysfunction after SCI.

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“…Transplantation of NS/PCs is promising treatment for SCI. [99][100][101][102][103] NS/PCs usual has been studied as a mean to replace the damaged neurons in SCI. However, increasing data showed that NSCs can promote motor functional recovery by modulating the host environment.…”

Section: Ns/pcs and Macrophage Polarizationmentioning

confidence: 99%

Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization

Zhang¹,

He²

2017

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Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

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Targeted Inhibition of Leucine-Rich Repeat and Immunoglobulin Domain-Containing Protein 1 in Transplanted Neural Stem Cells Promotes Neuronal Differentiation and Functional Recovery in Rats Subjected to Spinal Cord Injury*

Abstract: Our findings indicate that transplantation of LINGO-1-RNA interference-treated neural stem cells facilitates functional recovery after spinal cord injury and represents a promising potential strategy for the repair of spinal cord injury.

Cited by 35 publications

References 41 publications

MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury

MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury

Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury

Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization

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