Boundary Cap Neural Crest Stem Cells Promote Survival of Mutant SOD1 Motor Neurons

Aggarwal, Tanya; Hoeber, Jan; Ivert, Patrik; Vasylovska, Svitlana; Kozlova, Elena N.

doi:10.1007/s13311-016-0505-8

Cited by 12 publications

(16 citation statements)

References 46 publications

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“…Our study is supported by a recent report showing that neural crest-derived stem cells promote the survival of neurons under normal and oxidative stress conditions in a mutant neuron cell line [7]. However, the underlying mechanism requires further investigation.…”

Section: Discussionsupporting

confidence: 84%

NPC‐EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR‐210 Downstream Nox2 and VEGFR2 Pathways

Liu

Wang

Chen

et al. 2017

Oxidative Medicine and Cellular Longevity

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We have demonstrated that neural progenitor cells (NPCs) protect endothelial cells (ECs) from oxidative stress. Since exosomes (EXs) can convey the benefit of parent cells through their carried microRNAs (miRs) and miR-210 is ubiquitously expressed with versatile functions, we investigated the role of miR-210 in the effects of NPC-EXs on oxidative stress and dysfunction in ECs. NPCs were transfected with control and miR-210 scramble/inhibitor/mimic to generate NPC-EXscon, NPC-EXssc, NPC-EXsanti-miR-210, and NPC-EXsmiR-210. The effects of various NPC-EXs on angiotensin II- (Ang II-) induced reactive oxygen species (ROS) overproduction, apoptosis, and dysfunction, as well as dysregulation of Nox2, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 in ECs were evaluated. Results showed (1) Ang II-induced ROS overproduction, increase in apoptosis, and decrease in tube formation ability, accompanied with Nox2 upregulation and reduction of p-VEGFR2/VEGFR2 in ECs. (2) Compared to NPC-EXscon or NPC-EXssc, NPC-EXsanti-miR-210 were less whereas NPC-EXsmiR-210 were more effective on attenuating these detrimental effects induced by Ang II in ECs. (3) These effects of NPC-EXsanti-miR-210 and NPC-EXsmiR-210 were associated with the changes of miR-210, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 ratio in ECs. Altogether, the protective effects of NPC-EXs on Ang II-induced endothelial injury through miR-210 which controls Nox2/ROS and VEGF/VEGFR2 signals were studied.

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Section: Discussionsupporting

confidence: 84%

NPC‐EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR‐210 Downstream Nox2 and VEGFR2 Pathways

Liu

Wang

Chen

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…26 The animals were anesthetized by spontaneous inhalation of isoflurane. After dissection of the back muscles, the laminae of the cervical vertebrae were exposed and a partial laminectomy was made of cervical vertebrae 3 to 5.…”

Section: Surgerymentioning

confidence: 99%

The Effect of Mesoporous Silica Particles on Stem Cell Differentiation

Kozlova¹

2017

JSRT

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Abbreviations: bNCSC, boundary cap neural crest stem cell; DIFF, differentiation medium; eGFP, enhanced green fluorescent protein; GFAP, glial fibrillary acidic protein; Iba-1, ionized calcium binding adaptor molecule 1; MSP, mesoporous silica particle; PBS, phosphate buffered saline; TRITC, tetramethylrhodamine-5-(and 6)-isothiocyanate; Vol, volume; Wt, weight IntroductionMesoporous silica particles (MSPs) are characterized by ordered porosity, sharp pore size distributions, high internal surface areas, and large pore volumes. 1,2 Control over these structural parameters makes them an ideal candidate for drug encapsulation, perfectly suited to uptake and carry large amounts of drugs that then get released with constant concentration. [3][4][5] The release of the actives can be diffusion controlled or may be triggered by a change in media temperature or pH.6 Creation of simultaneous release profiles is possible by using different pore structures (e. g., 2D hexagonal and 3D cubic) that enable a continuous discharge of a fine tuned mixture of active drugs over a given period of time.MSPs have already shown potential for life science applications over traditional polymer based delivery systems. They offer increased bioavailability, biocompatibility, controlled and targeted release, reduced drug-drug interactions, the potential to deliver both lipophilic and hydrophilic drugs simultaneously, and the ability to customize release profiles for a combination of drugs. Moreover, nanoporous MSPs hold the potential to be not only a very efficient but also a cost effective drug delivery system. We previously showed that MSPs loaded with growth factor mimetics promote survival and differentiation of co-implanted neural stem cells, 7 indicating that the MSP delivery system can serve as a valuable tool for controlling differentiation of transplanted stem cells. Toxicological data from in vitro and in vivo studies suggest that unloaded MSPs have no observable harmful effects and are well tolerated. [8][9][10] However the possible influence of MSPs, used in our studies, on stem cell differentiation and on the non-neuronal response in the central nervous system has not been examined previously. Here we tested the effect of unloaded MSPs on in vitro differentiation of boundary cap neural crest stem cells (bNCSCs), a source of stem cells with remarkable therapeutic potential, and also analyzed the fate of MSPs at different time points after implantation into the spinal cord and on its surface. bNCSCs are neural crest derivatives that populate the entry/ exit points of spinal roots during embryonic development, 11,12 participate in cell migration and axon growth control at the spinal root-spinal cord interface, [13][14][15] AbstractStem cell transplantation is an attractive strategy to counteract the progression of neurodegenerative disorders and to replace lost neuronal cells. Despite successful generation of neuronal cell types in vitro, stem cell technology typically fails when applied in vivo. One of the reasons is lack of cont...

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“…To follow neuronal development and remodeling of neuronal extensions, we determined neurite outgrowth in cell cultures by tracing neurites and their branches using the stereological procedure, as described previously (Ronn et al, 2000). SOD1 G93A -expressing MNs grown in relatively pure cultures die rapidly over the 1st week (Aggarwal et al, 2017). Therefore, the first two assays were performed over the first 2 days of culture.…”

Section: Resultsmentioning

confidence: 99%

A VDAC1-Derived N-Terminal Peptide Inhibits Mutant SOD1-VDAC1 Interactions and Toxicity in the SOD1 Model of ALS

Shteinfer‐Kuzmine

Argueti

Gupta

et al. 2019

Front. Cell. Neurosci.

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Mutations in superoxide dismutase (SOD1) are the second most common cause of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease caused by the death of motor neurons in the brain and spinal cord. SOD1 neurotoxicity has been attributed to aberrant accumulation of misfolded SOD1, which in its soluble form binds to intracellular organelles, such as mitochondria and ER, disrupting their functions. Here, we demonstrate that mutant SOD1 binds specifically to the N-terminal domain of the voltage-dependent anion channel (VDAC1), an outer mitochondrial membrane protein controlling cell energy, metabolic and survival pathways. Mutant SOD1 G93A and SOD1 G85R , but not wild type SOD1, directly interact with VDAC1 and reduce its channel conductance. No such interaction with N-terminal-truncated VDAC1 occurs. Moreover, a VDAC1-derived N-terminal peptide inhibited mutant SOD1-induced toxicity. Incubation of motor neuron-like NSC-34 cells expressing mutant SOD1 or mouse embryonic stem cell-derived motor neurons with different VDAC1 N-terminal peptides resulted in enhanced cell survival. Taken together, our results establish a direct link between mutant SOD1 toxicity and the VDAC1 N-terminal domain and suggest that VDAC1 N-terminal peptides targeting mutant SOD1 provide potential new therapeutic strategies for ALS.

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Boundary Cap Neural Crest Stem Cells Promote Survival of Mutant SOD1 Motor Neurons

Cited by 12 publications

References 46 publications

NPC‐EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR‐210 Downstream Nox2 and VEGFR2 Pathways

NPC‐EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR‐210 Downstream Nox2 and VEGFR2 Pathways

The Effect of Mesoporous Silica Particles on Stem Cell Differentiation

A VDAC1-Derived N-Terminal Peptide Inhibits Mutant SOD1-VDAC1 Interactions and Toxicity in the SOD1 Model of ALS

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