Neural Stem/Progenitor Cells Promote Endothelial Cell Morphogenesis and Protect Endothelial Cells against Ischemia via HIF-1α-Regulated VEGF Signaling

Vascular cells provide a neural stem/progenitor cell (NSPC) niche that regulates expansion and differentiation of NSPCs within the germinal zones of the embryonic and adult brain under both physiologic and pathologic conditions. Here, we examined the NSPC—endothelial cell (NSPC/EC) interaction under conditions of ischemia, both in vitro and after intracerebral transplantation. In culture, embryonic mouse NSPCs supported capillary morphogenesis and protected ECs from cell death induced by serum starvation or by transient oxygen and glucose deprivation (OGD). Neural stem/progenitor cells constitutively expressed hypoxia-inducible factor 1α (HIF-1α) transcription factor and vascular endothelial growth factor (VEGF), both of which were increased approximately twofold after the exposure of NSPCs to OGD. The protective effects of NSPCs on ECs under conditions of serum starvation and hypoxia were blocked by pharmacological inhibitors of VEGF signaling, SU1498 and Flt-1-Fc. After intracerebral transplantation, NSPCs continued to express HIF-1α and VEGF, and promoted microvascular density after focal ischemia. These studies support a role for NSPCs in stabilization of vasculature during ischemia, mediated via HIF-1α-VEGF signaling pathways, and suggest therapeutic application of NSPCs to promote revascularization and repair after brain injury.

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Structurally Distinct LewisX Glycans Distinguish Subpopulations of Neural Stem/Progenitor Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m110.201095 ◽

2011 ◽

Vol 286 (18) ◽

pp. 16321-16331 ◽

Cited By ~ 29

Author(s):

Eva Hennen ◽

Tim Czopka ◽

Andreas Faissner

Keyword(s):

Progenitor Cells ◽

Carbohydrate Binding ◽

Neural Cells ◽

Stem Cell Markers ◽

Binding Assays ◽

Embryonic Mouse ◽

Isolation And Characterization ◽

Neural Stem Progenitor Cells

There is increasing evidence that the stem and progenitor cell population that builds the central nervous system is very heterogeneous. Stem cell markers with the potential to divide this cell pool into subpopulations with distinct characteristics are sparse. We were looking for new cell type-specific antigens to further subdivide the progenitor pool. Here, we introduce the novel monoclonal antibody clone 5750. We show that it specifically labels cell surfaces of neural stem and progenitor cells. When 5750-expressing cells were isolated by fluorescence-activated cell sorting from embryonic mouse brains, the sorted population showed increased neurosphere forming capacity and multipotency. Neurospheres generated from 5750-positive cells could self-renew and remained multipotent even after prolonged passaging. Carbohydrate binding assays revealed that the 5750 antibody specifically binds to LewisX-related carbohydrates. Interestingly, we found that the LewisX epitope recognized by clone 5750 differs from those detected by other anti-LewisX antibody clones like 487LeX, SSEA-1LeX, and MMALeX. Our data further reveal that individual anti-LewisX clones can be successfully used to label and deplete different subpopulations of neural cells in vivo and in vitro. In conclusion, we present a new tool for the isolation and characterization of neural subpopulations and provide insights into the complexity of cell surface glycosylation.

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CD60b: Enriching Neural Stem/Progenitor Cells from Rat Development into Adulthood

Stem Cells International ◽

10.1155/2017/5759490 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16

Author(s):

Fernanda Gubert ◽

Camila Zaverucha-do-Valle ◽

Michelle Furtado ◽

Pedro M. Pimentel-Coelho ◽

Nicoli Mortari ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Progenitor Cells ◽

System Development ◽

Nervous System Development ◽

Adult Brain ◽

Neurogenic Niche ◽

Neural Stem Progenitor Cells

CD60b antigens are highly expressed during development in the rat nervous system, while in the adult their expression is restricted to a few regions, including the subventricular zone (SVZ) around the lateral ventricles—a neurogenic niche in the adult brain. For this reason, we investigated whether the expression of C60b is associated with neural stem/progenitor cells in the SVZ, from development into adulthood. We performedin vitroandin vivoanalyses of CD60b expression at different stages and identified the presence of these antigens in neural stem/progenitor cells. We also observed that CD60b could be used to purify and enrich a population of neurosphere-forming cells from the developing and adult brain. We showed that CD60b antigens (mainly corresponding to ganglioside 9-O-acetyl GD3, a well-known molecule expressed during central nervous system development and mainly associated with neuronal migration) are also present in less mature cells and could be used to identify and isolate neural stem/progenitor cells during development and in the adult brain. A better understanding of molecules associated with neurogenesis may contribute not only to improve the knowledge about the physiology of the mammalian central nervous system, but also to find new treatments for regenerating tissue after disease or brain injury.

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Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

Journal of Endocrinology ◽

10.1677/joe-08-0495 ◽

2009 ◽

Vol 201 (1) ◽

pp. 141-150 ◽

Cited By ~ 42

Author(s):

N David Åberg ◽

Inger Johansson ◽

Maria A I Åberg ◽

Johan Lind ◽

Ulf E Johansson ◽

...

Keyword(s):

Cell Proliferation ◽

Corpus Callosum ◽

Progenitor Cells ◽

Parietal Cortex ◽

Cellular Proliferation ◽

Piriform Cortex ◽

Adult Brain ◽

Female Rats ◽

Igf I

IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily s.c. injections of bGH for either 6 or 28 days respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increase the number of BrdU-positive cells. 3H-thymidine incorporation in vitro revealed that 24 h of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells. This study shows for the first time that 1) peripheral bGH treatment increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.

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Reactive astrogliosis induces astrocytic differentiation of adult neural stem/progenitor cells in vitro

Journal of Neuroscience Research ◽

10.1002/jnr.21044 ◽

2006 ◽

Vol 84 (7) ◽

pp. 1415-1424 ◽

Cited By ~ 29

Author(s):

J. Faijerson ◽

R.B. Tinsley ◽

K. Apricó ◽

A. Thorsell ◽

C. Nodin ◽

...

Keyword(s):

Progenitor Cells ◽

Reactive Astrogliosis ◽

Astrocytic Differentiation ◽

Neural Stem Progenitor Cells

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Evaluation of the effects of riluzole on adult spinal cord‐derived neural stem/progenitor cells in vitro and in vivo

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2015.08.007 ◽

2015 ◽

Vol 47 (Part_B) ◽

pp. 140-146 ◽

Cited By ~ 5

Author(s):

Laureen D. Hachem ◽

Andrea J. Mothe ◽

Charles H. Tator

Keyword(s):

Spinal Cord ◽

Progenitor Cells ◽

Neural Stem Progenitor Cells ◽

Adult Spinal Cord

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Protective Effects ofN-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/764251 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Dongsun Park ◽

Kyungha Shin ◽

Ehn-Kyoung Choi ◽

Youngjin Choi ◽

Ja-Young Jang ◽

...

Keyword(s):

White Matter ◽

Progenitor Cells ◽

Hypoxic Ischemic Encephalopathy ◽

Oligodendrocyte Progenitor Cells ◽

Protective Effects ◽

Neonatal Rats ◽

Motor Functions ◽

Ischemic Encephalopathy

Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects ofN-acetyl-L-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats.Methods. Inin vitrostudy, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. Inin vivostudy, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed.Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE.Conclusion. The results indicate that NAC exerts neuroprotective effectsin vitroandin vivoby preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

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