scholarly journals The Neural Stem Cell Properties of PKD2L1+ Cerebrospinal Fluid-Contacting Neurons in vitro

2021 ◽  
Vol 15 ◽  
Author(s):  
Shuo Wang ◽  
Yuqi He ◽  
Huiqian Zhang ◽  
Li Chen ◽  
Liang Cao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Cerebrospinal Fluid ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Immunofluorescence Staining ◽  
Stem Cell Markers ◽  
Cord Injury

Cerebrospinal fluid-touching neurons (CSF-cNs) exist in the region surrounding the central canal of the spinal cord, which locate in the adult neurogenic niche. Previous research showed that CSF-cNs expressed the molecular markers of immature neural cells in vivo. Here, we explored the potential of CSF-cNs as neural stem cell in intro. We first found that PKD2L1+ CSF-cNs, isolating by FACS using the molecular marker PKD2L1 of CSF-cNs, expressed neural stem cells markers like Nestin, Sox2, and GFAP by immunofluorescence staining. PKD2L1+ CSF-cNs were able to form neurospheres and passaged in vitro. Immunofluorescence staining showed that the neurospheres forming by PKD2L1+ CSF-cNs also expressed neural stem cell markers Nestin, Sox2 and GFAP. The neurospheres expressed proliferation markers Ki67 and PCNA by immunofluorescence staining, indicating that the neurospheres forming by PKD2L1+ CSF-cNs were proliferative. The neurospheres, forming by CSF-cNs, had the ability of differentiation into neurons, astrocytes, and oligodendrocytes. Collectively, our data suggested that PKD2L1+ CSF-cNs have the properties of neural stem cells in vitro and may provide a promising approach for the repair of spinal cord injury.

scholarly journals Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury

2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
In Vivo Model ◽  
Human Neural Stem Cells ◽  
Cord Injury

Multifunctional silica-coated iron oxide nanoparticles: a facile four-in-one system for in situ study of neural stem cell harvesting

2014 ◽  
Vol 175 ◽  
pp. 13-26 ◽  
Author(s):  
Yung-Kang Peng ◽  
Cathy N. P. Lui ◽  
Tsen-Hsuan Lin ◽  
Chen Chang ◽  
Pi-Tai Chou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Iron Oxide ◽  
Magnetic Resonance ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Cell Therapies ◽  
Bimodal Imaging

Neural stem cells (NSCs), which generate the main phenotypes of the nervous system, are multipotent cells and are able to differentiate into multiple cell types via external stimuli from the environment. The extraction, modification and re-application of NSCs have thus attracted much attention and raised hopes for novel neural stem cell therapies and regenerative medicine. However, few studies have successfully identified the distribution of NSCs in a live brain and monitored the corresponding extraction processes both in vitro and in vivo. To address those difficulties, in this study multi-functional uniform nanoparticles comprising an iron oxide core and a functionalized silica shell (Fe3O4@SiO2(FITC)-CD133, FITC: a green emissive dye, CD133: anti-CD133 antibody) have been strategically designed and synthesized for use as probe nanocomposites that provide four-in-one functionality, i.e., magnetic agitation, dual imaging (both magnetic resonance and optical) and specific targeting. It is shown that these newly synthesized Fe3O4@SiO2(FITC)-CD133 particles have clearly demonstrated their versatility in various applications. (1) The magnetic core enables magnetic cell collection and T2 magnetic resonance imaging. (2) The fluorescent FITC embedded in the silica framework enables optical imaging. (3) CD133 anchored on the outermost surface is demonstrated to be capable of targeting neural stem cells for cell collection and bimodal imaging.

Transplantation of embryonic stem cell-derived neural stem cells for spinal cord injury in adult mice

2005 ◽  
Vol 27 (8) ◽  
pp. 812-819 ◽  
Author(s):  
Hajime Kimura ◽  
Masahide Yoshikawa ◽  
Ryousuke Matsuda ◽  
Hayato Toriumi ◽  
Fumihiko Nishimura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Adult Mice ◽  
Cord Injury

scholarly journals Rosiglitazone Ameliorates Spinal Cord Injury via Inhibiting Mitophagy and Inflammation of Neural Stem Cells

2022 ◽  
Vol 2022 ◽  
pp. 1-22
Author(s):  
Qingqi Meng ◽  
Zhiteng Chen ◽  
Qingyuan Gao ◽  
Liqiong Hu ◽  
Qilong Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Atp Production ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Underlying Mechanisms

Background. Neurodegenerative diseases, such as Alzheimer’s disease, and traumatic brain and spinal cord injury (SCI) are prevalent in clinical practice. Inhibition of hyperactive inflammation and proliferation of endogenous neural stem cells (NSCs) is a promising treatment strategy for SCI. Our previous studies demonstrated the beneficial effects of rosiglitazone (Rosi) on SCI, but its roles in inflammation inhibition and proliferation of NSCs are unknown. Methods. SCI in a rat model was established, and the effects of Rosi on motor functions were assessed. The effects of Rosi on NSC proliferation and the underlying mechanisms were explored in details. Results. We showed that Rosi ameliorated impairment of moto functions in SCI rats, inhibited inflammation, and promoted proliferation of NSCs in vivo. Rosi increased ATP production through enhancing glycolysis but not oxidative phosphorylation. Rosi reduced mitophagy by downregulating PTEN-induced putative kinase 1 (PINK1) transcription to promote NSC proliferation, which was effectively reversed by an overexpression of PINK1 in vitro. Through KEGG analysis and experimental validations, we discovered that Rosi reduced the expression of forkhead box protein O1 (FOXO1) which was a critical transcription factor of PINK1. Three FOXO1 consensus sequences (FCSs) were found in the first intron of the PINK1 gene, which could be potentially binding to FOXO1. The proximal FCS (chr 5: 156680169–156680185) from the translation start site exerted a more significant influence on PINK1 transcription than the other two FCSs. The overexpression of FOXO1 entirely relieved the inhibition of PINK1 transcription in the presence of Rosi. Conclusions. Besides inflammation inhibition, Rosi suppressed mitophagy by reducing FOXO1 to decrease the transcription of PINK1, which played a pivotal role in accelerating the NSC proliferation.

scholarly journals GP.04 Smart human neural stem cells to degrade scar and optimize regeneration after traumatic cervical spinal cord injury

2018 ◽  
Vol 45 (s2) ◽  
pp. S9-S9
Author(s):  
CS Ahuja ◽  
M Khazaei ◽  
P Chan ◽  
J Bhavsar ◽  
Y Yao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Chronic Injury ◽  
Long Distance ◽  
Degrading Enzyme ◽  
Genetically Engineer ◽  
Cord Injury

Background: Human induced pluripotent stem cell-derived neural stem cells (hiPS-NSCs) represent an exciting therapeutic approach for traumatically spinal cord injury (SCI). Unfortunately, most patients are the in chronic injury phase where a dense perilesional chondroitin sulfate proteoglycan (CSPG) scar significantly hinders regeneration. CSPG-degrading enzymes can enhance NSC-mediated recovery, however, nonspecific intrathecal administration causes off-target effects. We aimed to genetically engineer hiPS-NSCs to express a scar-degrading ENZYME into their local environment to enhance functional recovery. Methods: A bicistronic scar-degrading ENZYME and RFP reporter vector was non-virally integrated into hiPS-NSCs and monoclonalized. ENZYME activity was assessed by WST-1 and DMMB biochemical assays and an in vitro CSPG spot assay with hiPS-NSC-derived neurons. To assess in vivo efficacy, T-cell deficient rats (N=60) with chronic (8wk) C6-7 SCIs were randomized to receive (1)SMaRT cells, (2)hiPS-NSCs, (3)vehicle, or (4)sham surgery. Results: SMaRT cells retained key hiPS-NSC characteristics while stably expressing ENZYME. The expressed ENZYME could appropriately degrade in vitro and ex vivo CSPGs. While blinded neurobehavioural and immunohistochemical assessments are ongoing at 40wks post-injury, an interim analysis demonstrated human cells extending remarkably long (≥20,000µm) axons along host white matter tracts. Conclusions: This work provides exciting proof-of-concept data that genetically-engineered SMaRT cells can degrade CSPGs and human NSCs can extend long-distance processes in chronic SCI.

scholarly journals Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

2021 ◽  
Vol 22 (11) ◽  
pp. 5966
Author(s):  
Pablo Bonilla ◽  
Joaquim Hernandez ◽  
Esther Giraldo ◽  
Miguel A. González-Pérez ◽  
Ana Alastrue-Agudo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Neural Function ◽  
Neuroprotective Effects ◽  
Cord Injury

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.

scholarly journals Rapid and Efficient Differentiation of Rodent Neural Stem Cells into Oligodendrocyte Progenitor Cells

2019 ◽  
Vol 41 (1-2) ◽  
pp. 79-93 ◽  
Author(s):  
Shen Li ◽  
Jiao Zheng ◽  
Linlin Chai ◽  
Mengsi Lin ◽  
Ruocheng Zeng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Progenitor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Cord Injury

Oligodendrocyte progenitor cells (OPCs) may have beneficial effects in cell replacement therapy of neurodegenerative disease owing to their unique capability to differentiate into myelinogenic oligodendrocytes (OLs) in response to extrinsic signals. Therefore, it is of significance to establish an effective differentiation methodology to generate highly pure OPCs and OLs from some easily accessible stem cell sources. To achieve this goal, in this study, we present a rapid and efficient protocol for oligodendroglial lineage differentiation from mouse neural stem cells (NSCs), rat NSCs, or mouse embryonic stem cell-derived neuroepithelial stem cells. In a defined culture medium containing Smoothened Agonist, basic fibroblast growth factor, and platelet-derived growth factor-AA, OPCs could be generated from the above stem cells over a time course of 4–6 days, achieving a cell purity as high as ∼90%. In particular, these derived OPCs showed high expandability and could further differentiate into myelin basic protein-positive OLs within 3 days or alternatively into glial fibrillary acidic protein-positive astrocytes within 7 days. Furthermore, transplantation of rodent NSC-derived OPCs into injured spinal cord indicated that it is a feasible strategy to treat spinal cord injury. Our results suggest a differentiation strategy for robust production of OPCs and OLs from rodent stem cells, which could provide an abundant OPC source for spinal cord injury.

scholarly journals Spinal cord neural stem cells heterogeneity in postnatal development

STEMedicine ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. e19
Author(s):  
Jelena Ban ◽  
Miranda Mladinic
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Types ◽  
In Vitro Models ◽  
Cell Potential ◽  
Neurogenic Niche ◽  
The Brain

Neural stem cells are capable of generating new neurons during development as well as in the adulthood and represent one of the most promising tools to replace lost or damaged neurons after injury or neurodegenerative disease. Unlike the brain, neurogenesis in the adult spinal cord is poorly explored and the comprehensive characterization of the cells that constitute stem cell neurogenic niche is still missing. Moreover, the terminology used to specify developmental and/or anatomical CNS regions, where neurogenesis in the spinal cord occurs, is not consensual and the analogy with the brain is often unclear. In this review, we will try to describe the heterogeneity of the stem cell types in the spinal cord ependymal zone, based on their origin and stem cell potential. We will also consider specific animal in vitro models that could be useful to identify “the right” stem cell candidate for cell replacement therapies.   

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