Neural stem cell differentiation into mature neurons: Mechanisms of regulation and biotechnological applications

Vieira, Mariana Sousa; Santos, Anderson K.; Vasconcellos, Rebecca; Goulart, Vânia Aparecida Mendes; Parreira, Ricardo Cambraia; Kihara, Alexandre Hiroaki; Ulrich, Henning; Resende, Rodrigo R.

doi:10.1016/j.biotechadv.2018.08.002

Cited by 133 publications

(86 citation statements)

References 341 publications

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“…In Equation (22), the eigenvalue λ = f 66 is distinctly positive, by Proposition 2. Thus, J(E R ) has at least one positive root and, so, the equilibrium point E R is unstable [44].…”

Section: Proofmentioning

confidence: 83%

“…We take R 1 < R 2 when the rate of proinflammation cytokines, R 1 , is at a lower rate than the rate of anti-inflammation cytokines, R 2 in the recovery stage in the SMNR model. Neural stem cells in the subventricular zone from the adult mammalian brain give rise to neuroblasts, which migrate to the injury region and generate new cells [22,28,41]. Microglia have a positive and negative impact on generating neural stem cells [42].…”

Section: Mathematical Modelsmentioning

confidence: 99%

“…In adult brains, neural stem cells (which are active throughout life) are capable of generating different cells [22,23]. Neurogenesis continues for the duration of life in the subventricular zone in all mammalian types, generating new neural stem cells during the recovery stage after ischemic stroke [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…Neurogenesis continues for the duration of life in the subventricular zone in all mammalian types, generating new neural stem cells during the recovery stage after ischemic stroke [24][25][26][27]. Neural stem cells appear to have many important roles, such as self-renewal and multipotency, replacement of the dead cells, and inhibition of inflammation [22,[28][29][30]. However, endogenous neural stem cells may not be able to generate enough cells to repair the neurological damage caused by a major disease such as stroke [31].…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Modelling of Interactions between Microglia and Endogenous Neural Stem Cells in the Brain during a Stroke

2020

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In this paper, we study the interactions between microglia and neural stem cells and the impact of these interactions on the brain cells during a stroke. Microglia cells, neural stem cells, the damage on brain cells from the stroke and the impacts these interactions have on living brain cells are considered in the design of mathematical models. The models consist of ordinary differential equations describing the effects of microglia on brain cells and the interactions between microglia and neural stem cells in the case of a stroke. Variables considered include: resident microglia, classically activated microglia, alternatively activated microglia, neural stem cells, tissue damage on cells in the brain, and the impacts these interactions have on living brain cells. The first model describes what happens in the brain at the stroke onset during the first three days without the generation of any neural stem cells. The second model studies the dynamic effect of microglia and neural stem cells on the brain cells following the generation of neural stem cells and potential recovery after this stage. We look at the stability and the instability of the models which are both studied analytically. The results show that the immune cells can help the brain by cleaning dead cells and stimulating the generation of neural stem cells; however, excessive activation may cause damage and affect the injured region. Microglia have beneficial and harmful functions after ischemic stroke. The microglia stimulate neural stem cells to generate new cells that substitute dead cells during the recovery stage but sometimes the endogenous neural stem cells are highly sensitive to inflammatory in the brain.

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“…In Equation (22), the eigenvalue λ = f 66 is distinctly positive, by Proposition 2. Thus, J(E R ) has at least one positive root and, so, the equilibrium point E R is unstable [44].…”

Section: Proofmentioning

confidence: 83%

Section: Mathematical Modelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic Modelling of Interactions between Microglia and Endogenous Neural Stem Cells in the Brain during a Stroke

2020

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“…Fate determination and differentiation of NSCs is a complex physiological procedure that dependent on intrinsic and extrinsic cues, such as growth factors, transcription factors and signaling pathways activation [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Potential role of heat shock protein 90 in regulation of hyperthermia-driven differentiation of neural stem cells

Wang

Zhuo

et al. 2019

Preprint

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Objective: Our previous studies indicated that hyperthermia may play a role in differentiation of neural stem cells and that hypoxia inducible factor-1(HIF-1) was critical in this process. Heat shock protein 90 (Hsp90) is one of the most common heat-related proteins and involved in HIF-1 expression by regulating its activity and stabilization. Here, we hypothesized that HSP90 may be involved in regulation of hyperthermia-driven differentiation of neural stem cells(NSCs). We also investigated whether the HSP90 activity exert its regulatory action via HIF-1 pathway and the transcriptional level of the target genes of HIF-1. Method: The cultured NSCs were divided into three groups: an hyperthermic treatment group(40NSC) which NSCs was induced under 40˚C temperature; a control group(37NSC) which NSCs was induced under 37˚C temperature; an hyperthermic treatment and HSP90-inhibited group(40NSC+GA) which NSCs was induced with 0.5μM HSP90 inhibitor Geldanamycin(GA) under 40˚C temperature. We examined cells HSPɑ and HIF-1ɑ expression during a time window of 5 days(12h, 1d, 3d, 5d) post-differentiation. The expression HSPα, HIF-1α, VEGF (vascular endothelial growth factor) and erythmpoietin(EPO) of during a time window was evaluated by RT-qPCR. The proportion of Tuj-1 positive differentiated cells were observed by flow cytometry. Result: Hyperthermia promoted neuronal differentiation of NSC, and this effect could be blocked by HSP90 inhibitor GA. We observed the up-regulation of HSP90 during hyperthermia treatment, and that the protein levels of HIF-1α changed depending of the GA treatment. GA could not inhibited HSP90α expression but suppressed HSP activity and decreased the expression HIF-1α protein. Inhibition of HIF-1α expression by GA could consequently affect expression of its targeted genes such as VEGF and EPO. Conclusion: Hyperthermia promote differentiation of NSCs into neurons.HSP90 involved in the regulation of hyperthermia-driven differentiation of NSC, and the mechanism is related to HIF-1α and its downstream gene activation.

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Engineering Tissues of the Central Nervous System: Interfacing Conductive Biomaterials with Neural Stem/Progenitor Cells

Bierman-Duquette

Safarians

Huang

et al. 2021

Adv Healthcare Materials

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Conductive biomaterials provide an important control for engineering neural tissues, where electrical stimulation can potentially direct neural stem/progenitor cell (NS/PC) maturation into functional neuronal networks. It is anticipated that stem cell-based therapies to repair damaged central nervous system (CNS) tissues and ex vivo, "tissue chip" models of the CNS and its pathologies will each benefit from the development of biocompatible, biodegradable, and conductive biomaterials. Here, technological advances in conductive biomaterials are reviewed over the past two decades that may facilitate the development of engineered tissues with integrated physiological and electrical functionalities. First, one briefly introduces NS/PCs of the CNS. Then, the significance of incorporating microenvironmental cues, to which NS/PCs are naturally programmed to respond, into biomaterial scaffolds is discussed with a focus on electrical cues. Next, practical design considerations for conductive biomaterials are discussed followed by a review of studies evaluating how conductive biomaterials can be engineered to control NS/PC behavior by mimicking specific functionalities in the CNS microenvironment. Finally, steps researchers can take to move NS/PC-interfacing, conductive materials closer to clinical translation are discussed.

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Neural stem cell differentiation into mature neurons: Mechanisms of regulation and biotechnological applications

Cited by 133 publications

References 341 publications

Dynamic Modelling of Interactions between Microglia and Endogenous Neural Stem Cells in the Brain during a Stroke

Dynamic Modelling of Interactions between Microglia and Endogenous Neural Stem Cells in the Brain during a Stroke

Potential role of heat shock protein 90 in regulation of hyperthermia-driven differentiation of neural stem cells

Engineering Tissues of the Central Nervous System: Interfacing Conductive Biomaterials with Neural Stem/Progenitor Cells

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