Neural stem cell-laden 3D bioprinting of polyphenol-doped electroconductive hydrogel scaffolds for enhanced neuronal differentiation

Abstract Background Stroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their antioxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI). Methods We investigated MCPs’ function in differentiation of NSCs in vitro experiments. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of ischemia / reperfusion injury (IRI). We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation were also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1. Results MCPs had no effects on the differentiation of neural stem cells under physiological conditions, while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCPs-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs. Conclusion Our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.

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Functionalization of Electrospun Nanofibers and Fiber Alignment Enhance Neural Stem Cell Proliferation and Neuronal Differentiation

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.580135 ◽

2020 ◽

Vol 8 ◽

Author(s):

Miriam C. Amores de Sousa ◽

Carlos A. V. Rodrigues ◽

Inês A. F. Ferreira ◽

Maria Margarida Diogo ◽

Robert J. Linhardt ◽

...

Keyword(s):

Cell Proliferation ◽

Stem Cell ◽

Neuronal Differentiation ◽

Neural Stem Cell ◽

Electrospun Nanofibers ◽

Fiber Alignment ◽

Stem Cell Proliferation ◽

Neural Stem Cell Proliferation

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Downregulation of an Evolutionary Young miR-1290 in an iPSC-Derived Neural Stem Cell Model of Autism Spectrum Disorder

Stem Cells International ◽

10.1155/2019/8710180 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Dalia Moore ◽

Brittney M. Meays ◽

Lepakshe S. V. Madduri ◽

Farah Shahjin ◽

Subhash Chand ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Stem Cell ◽

Neuronal Differentiation ◽

Neural Stem Cell ◽

Cell Model ◽

Critical Role ◽

Induced Pluripotent Stem Cell ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Induced Pluripotent

The identification of several evolutionary young miRNAs, which arose in primates, raised several possibilities for the role of such miRNAs in human-specific disease processes. We previously have identified an evolutionary young miRNA, miR-1290, to be essential in neural stem cell proliferation and neuronal differentiation. Here, we show that miR-1290 is significantly downregulated during neuronal differentiation in reprogrammed induced pluripotent stem cell- (iPSC-) derived neurons obtained from idiopathic autism spectrum disorder (ASD) patients. Further, we identified that miR-1290 is actively released into extracellular vesicles. Supplementing ASD patient-derived neural stem cells (NSCs) with conditioned media from differentiated control-NSCs spiked with “artificial EVs” containing synthetic miR-1290 oligonucleotides significantly rescued differentiation deficits in ASD cell lines. Based on our earlier published study and the observations from the data presented here, we conclude that miR-1290 regulation could play a critical role during neuronal differentiation in early brain development.

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