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

Wang, Lei; Gu, Sujie; Gan, Jinlu; Tian, Yi; Zhang, Fangcheng; Zhao, Hongyang; Lei, Deqiang

doi:10.3389/fncel.2021.773375

Cited by 26 publications

(21 citation statements)

References 53 publications

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“…Furthermore, VitD can enhance neural stem cell proliferation and differentiation into neurons and oligodendrocytes ( 85 , 86 ). It would be interesting to explore whether VitD could interact with neural stem cells to promote neurons and myelin regeneration after SCI via enhancing and modulating endogenous neurogenesis ( 87 – 89 ). Recent literature indicated that small molecules combined with collagen hydrogel directed neurogenesis and migration of neural stem cells after implantation in the lesioned spinal cord ( 90 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Wang

Gan²,

Wu³

et al. 2023

Front. Nutr.

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Vitamin D (VitD) insufficiency is a worldwide health problem and affects billions of people. Spinal cord injury (SCI) patients seem more susceptible to developing suboptimal levels of VitD. However, the literature regarding its impact on the prognosis of SCI is limited. Thus, in this review, we systematically investigated the published studies via a combination of keywords associated with SCI and VitD in four medical databases (Medline, Embase, Scopus, and Web of Science). All included studies were analyzed, and selected clinical data on the prevalence of VitD insufficiency (serum 25-hydroxyvitamin D < 30 ng/ml) and deficiency (serum 25-hydroxyvitamin D < 20 ng/ml) were collected for further meta-analysis via random effects. Through literature review, a total of 35 studies were eligible and included. The meta-analysis of VitD status (13 studies, 1,962 patients) indicated high prevalence of insufficiency (81.6% [75.7, 87.5]) and deficiency (52.5% [38.1, 66.9]) after SCI. Besides, low levels of VitD were reported to be associated with a higher risk of skeletal diseases, venous thromboembolism, psychoneurological syndromes, and chest illness after injury. Existing literature suggested that supplemental therapy might act as an adjuvant treatment to facilitate post-injury rehabilitation. Non-human experimental studies highlighted the neuroprotective effect of VitD, which was associated with enhancing axonal and neuronal survival, suppressing neuroinflammation, and modulating autophagy. Therefore, the current evidence suggests that the prevalence of VitD insufficiency is high in the SCI population, and low-level VitD may impair functional restoration after SCI. VitD supplemental treatment may have potential benefits to accelerate rehabilitation in mechanistically related processes after SCI. However, due to the limitation of the available evidence, more well-designed randomized controlled trials and mechanism experimental research are still needed to validate its therapeutic effect, elucidate its neuroprotective mechanism, and develop novel treatments.

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Section: Discussionmentioning

confidence: 99%

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Wang

Gan²,

Wu³

et al. 2023

Front. Nutr.

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“…We found that the presence of either EGF/bFGF or NGF is essential for NPSC EV bioactivity, with NGF alone producing more consistently enhanced PC-12 neurite outgrowth compared to EGF/bFGF alone. Recently, engineering NPSCs to overexpress NGF was shown to enhance SCI recovery in mice following transplantation of these cells into the lesion area 49 . A well-recognized advantage of EVs is their ability to transport and deliver bioactive cargo.…”

Section: Discussionmentioning

confidence: 99%

Differentiation state and culture conditions impact neural stem/progenitor cell-derived extracellular vesicle bioactivity

Dutta

Pirolli

Levy

et al. 2023

Preprint

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Extracellular vesicles (EVs) derived from neural progenitor/stem cells (NPSCs) have shown promising efficacy in a variety of preclinical models. However, NPSCs lack critical neuroregenerative functionality such as myelinating capacity. Further, culture conditions used in NPSC EV production lack standardization and identification of optimal conditions for NPSC EV neurogenic bioactivity. Here, we assessed whether further differentiated oligodendrocyte precursor cells (OPCs) and immature oligodendrocytes (iOLs) that give rise to mature myelinating oligodendrocytes could yield EVs with neurotherapeutic properties comparable or superior to those from NPSCs as well as mesenchymal stromal cells (MSCs), as MSC EVs are also commonly reported to have neurotherapeutic activity. We additionally examined the effects of four different extracellular matrix (ECM) coating materials (laminin, fibronectin, Matrigel, and collagen IV) and the presence or absence of growth factors (EGF, bFGF, and NGF) in cell culture on the ultimate properties of EVs. The data show that OPC EVs and iOL EVs performed similarly to NPSC EVs in PC-12 proliferation and RAW264.7 mouse macrophage anti-inflammatory assays, but NPSC EVs performed better in a PC-12 neurite outgrowth assay. Additionally, the presence of nerve growth factor (NGF) in culture was found to be maximize NPSC EV bioactivity among the conditions tested. NPSC EVs produced under rationally-selected culture conditions (fibronectin + NGF) enhanced axonal regeneration and muscle reinnervation in a rat nerve crush injury model. These results highlight the impact of culture conditions on NPSC EV neuroregenerative bioactivity, thus providing additional rationale for standardization and optimization of culture conditions for NPSC EV production.

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“…These “primed” NSCs showed decreased Notch and BMP signaling and an increase in lineage-specific transcription factors and protein synthesis (i.e., EGFR, cyclin-dependent kinase 2 (CDK2)) [ 80 ]. With regard to neural repair, modulating the activation state of forebrain NSCs by pulling them out of quiescence has been shown to result from injury alone, as well as following the administration of growth factors, cytokines and drugs [ 61 , 92 , 93 , 94 , 95 , 96 ] Indeed, brain repair and improved functional outcomes have been correlated with the activation of endogenous NSCs [ 91 , 97 , 98 , 99 ].…”

Section: Adult Neural Stem Cells: a Heterogeneous Population Of Cellsmentioning

confidence: 99%

Regulating Endogenous Neural Stem Cell Activation to Promote Spinal Cord Injury Repair

Gilbert

Lakshman

Lau

et al. 2022

Cells

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Spinal cord injury (SCI) affects millions of individuals worldwide. Currently, there is no cure, and treatment options to promote neural recovery are limited. An innovative approach to improve outcomes following SCI involves the recruitment of endogenous populations of neural stem cells (NSCs). NSCs can be isolated from the neuroaxis of the central nervous system (CNS), with brain and spinal cord populations sharing common characteristics (as well as regionally distinct phenotypes). Within the spinal cord, a number of NSC sub-populations have been identified which display unique protein expression profiles and proliferation kinetics. Collectively, the potential for NSCs to impact regenerative medicine strategies hinges on their cardinal properties, including self-renewal and multipotency (the ability to generate de novo neurons, astrocytes, and oligodendrocytes). Accordingly, endogenous NSCs could be harnessed to replace lost cells and promote structural repair following SCI. While studies exploring the efficacy of this approach continue to suggest its potential, many questions remain including those related to heterogeneity within the NSC pool, the interaction of NSCs with their environment, and the identification of factors that can enhance their response. We discuss the current state of knowledge regarding populations of endogenous spinal cord NSCs, their niche, and the factors that regulate their behavior. In an attempt to move towards the goal of enhancing neural repair, we highlight approaches that promote NSC activation following injury including the modulation of the microenvironment and parenchymal cells, pharmaceuticals, and applied electrical stimulation.

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

Cited by 26 publications

References 53 publications

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Differentiation state and culture conditions impact neural stem/progenitor cell-derived extracellular vesicle bioactivity

Regulating Endogenous Neural Stem Cell Activation to Promote Spinal Cord Injury Repair

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