scholarly journals Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix

2019 ◽  
Author(s):  
Disha Sood ◽  
Dana M. Cairns ◽  
Jayanth M. Dabbi ◽  
Charu Ramakrishnan ◽  
Karl Deisseroth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Tissue ◽  
Fetal Brain ◽  
Functional Differentiation ◽  
Adult Brain ◽  
Human Neural Stem Cells ◽  
Functional Maturation ◽  
Enriched Cultures

AbstractBrain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and astrocytes. Particularly, fetal brain tissue-derived ECM supported long-term maintenance of differentiated neurons, demonstrated by morphology, gene expression and secretome profiling. Astrocytes were evident within the second month of differentiation, and reactive astrogliosis was inhibited in brain ECM-enriched cultures when compared to unsupplemented cultures. Functional maturation of the differentiated hiNSCs within fetal ECM-enriched cultures was confirmed by calcium signaling and unsupervised cluster analysis. Additionally, the study identified native biochemical cues in decellularized ECM with notable comparisons between fetal and adult brain-derived ECMs. The development of novel brain-specific biomaterials for generating mature in vitro brain models provides an important path forward for interrogation of neuron-glia interactions.

scholarly journals Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Disha Sood ◽  
Dana M. Cairns ◽  
Jayanth M. Dabbi ◽  
Charu Ramakrishnan ◽  
Karl Deisseroth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Tissue ◽  
Fetal Brain ◽  
Functional Differentiation ◽  
Adult Brain ◽  
Human Neural Stem Cells ◽  
Functional Maturation ◽  
Enriched Cultures

AbstractBrain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and astrocytes. Particularly, fetal brain tissue-derived ECM supported long-term maintenance of differentiated neurons, demonstrated by morphology, gene expression and secretome profiling. Astrocytes were evident within the second month of differentiation, and reactive astrogliosis was inhibited in brain ECM-enriched cultures when compared to unsupplemented cultures. Functional maturation of the differentiated hiNSCs within fetal ECM-enriched cultures was confirmed by calcium signaling and spectral/cluster analysis. Additionally, the study identified native biochemical cues in decellularized ECM with notable comparisons between fetal and adult brain-derived ECMs. The development of novel brain-specific biomaterials for generating mature in vitro brain models provides an important path forward for interrogation of neuron-glia interactions.

scholarly journals Neural stem cells: involvement in adult neurogenesis and CNS repair

2008 ◽  
Vol 363 (1500) ◽  
pp. 2111-2122 ◽  
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Adult Neurogenesis ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Therapeutic Interventions ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.

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

scholarly journals Icariin promotes cell proliferation and regulates gene expression in human neural stem cells in vitro

2016 ◽  
Vol 14 (2) ◽  
pp. 1316-1322 ◽  
Author(s):  
Pan Yang ◽  
Yun-Qian Guan ◽  
Ya-Li Li ◽  
Li Zhang ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells

scholarly journals Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro

2015 ◽  
Vol 35 (5) ◽  
pp. 2019-2032 ◽  
Author(s):  
Wei Cheng ◽  
Pingping Yu ◽  
Li Wang ◽  
Changbo Shen ◽  
Xiaosong Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Sonic Hedgehog ◽  
Glucose Deprivation ◽  
Adult Brain ◽  
Immunocytochemical Staining ◽  
Oxygen Glucose Deprivation ◽  
Shh Signaling ◽  
Gli 1

Background/Aims: There is interest in drugs and rehabilitation methods to enhance neurogenesis and improve neurological function after brain injury or degeneration. Resveratrol may enhance hippocampal neurogenesis and improve hippocampal atrophy in chronic fatigue mice and prenatally stressed rats. However, its effect and mechanism of neurogenesis after stroke is less well understood. Sonic hedgehog (Shh) signaling is crucial for neurogenesis in the embryonic and adult brain, but relatively little is known about the role of Shh signaling in resveratrol-enhanced neurogenesis after stroke. Methods: Neural stem cells (NSCs) before oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro were pretreated with resveratrol with or without cyclopamine. Survival and proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical staining. The expressions and activity of signaling proteins and mRNAs were detected by immunocytochemistry, Western blotting, and RT-PCR analysis. Results: Resveratrol significantly increased NSCs survival and proliferation in a concentration-dependent manner after OGD/R injury in vitro. At the same time, the expression of Patched-1, Smoothened (Smo), and Gli-1 proteins and mRNAs was upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a Smo inhibitor. Conclusion: Shh signaling mediates resveratrol to increase NSCs proliferation after OGD/R injury in vitro.

Genome wide expression analysis of human neural stem cells in vitro

2006 ◽  
Vol 198 (2) ◽  
pp. 593
Author(s):  
D.R. Wakeman ◽  
E.Y. Snyder ◽  
D.E. Redmond ◽  
J.F. Loring ◽  
F.J. Mueller
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Expression Analysis ◽  
Human Neural Stem Cells ◽  
Genome Wide ◽  
Genome Wide Expression

scholarly journals Modelling West Nile Virus and Usutu Virus Pathogenicity in Human Neural Stem Cells

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 882 ◽  
Author(s):  
Silvia Riccetti ◽  
Alessandro Sinigaglia ◽  
Giovanna Desole ◽  
Norbert Nowotny ◽  
Marta Trevisan ◽  
...  
Keyword(s):  
Stem Cells ◽  
West Nile Virus ◽  
Neural Stem Cells ◽  
Clinical Manifestations ◽  
Fetal Brain ◽  
Adult Brain ◽  
Interferon Response ◽  
Type I ◽  
West Nile ◽  
Usutu Virus

West Nile virus (WNV) and Usutu virus (USUV) are genetically related neurotropic mosquito-borne flaviviruses, which frequently co-circulate in nature. Despite USUV seeming to be less pathogenic for humans than WNV, the clinical manifestations induced by these two viruses often overlap and may evolve to produce severe neurological complications. The aim of this study was to investigate the effects of WNV and USUV infection on human induced pluripotent stem cell-derived neural stem cells (hNSCs), as a model of the neural progenitor cells in the developing fetal brain and in adult brain. Zika virus (ZIKV), a flavivirus with known tropism for NSCs, was used as the positive control. Infection of hNSCs and viral production, effects on cell viability, apoptosis, and innate antiviral responses were compared among viruses. WNV displayed the highest replication efficiency and cytopathic effects in hNSCs, followed by USUV and then ZIKV. In these cells, both WNV and USUV induced the overexpression of innate antiviral response genes at significantly higher levels than ZIKV. Expression of interferon type I, interleukin-1β and caspase-3 was significantly more elevated in WNV- than USUV-infected hNSCs, in agreement with the higher neuropathogenicity of WNV and the ability to inhibit the interferon response pathway.

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