A new method for the rapid and long term growth of human neural precursor cells

Svendsen, Clive N.; Borg, Melanie G. Ter; Armstrong, Richard J. E.; Rosser, Anne Elizabeth; Chandran, Siddharthan; Ostenfeld, Thor; Caldwell, Maeve A.

doi:10.1016/s0165-0270(98)00126-5

Cited by 552 publications

(513 citation statements)

References 31 publications

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“…Our unique method of hNPC propagation permits constant cell/cell contact and eliminates exposure to serum or trypsin and stress from single-cell dissociation. 18 This technique may reduce the possibility of immortalization events seen in human embryonic stem cells associated with repetitive trypsin treatment and dissociation to single cells. 45 We have previously shown that hNPC grown as neurospheres without dissociation during passage do not express telomerase required for immortalization 46 and therefore have a finite lifespan in culture (Wright et al, in preparation).…”

Section: Discussionmentioning

confidence: 99%

“…Neurosphere colonies rapidly formed and were expanded by chopping using an automated tissue chopper as described in detail previously. 18 At 10 weeks the cells were switched to medium containing LIF (Chemicon, 10 ng/ml) and under these conditions the cultures could be grown for at least another 30 weeks in a relatively stable form based on gene expression patterns and differentiation potential. 19 …”

Section: Cell Growthmentioning

confidence: 99%

“…These cells can be isolated from post-mortem fetal brain tissue and expanded for significant periods of time in culture. 18,19 hNPC react very differently from fibroblasts or primary fetal tissue following transplantation. Rather than forming a transplant core of non-migrating cells, a single deposit can fill almost the entire striatum.…”

Section: Introductionmentioning

confidence: 99%

“…20,21 Furthermore, a number of reports have shown that hNPC can differentiate into both astrocytes and neurons following transplantation into the nervous system. 18,20,[22][23][24][25] We have previously shown that non-modified hNPC can lead to functional restoration in a model of Huntington's disease, potentially through neuroprotective effects on dying striatal neurons. 21 However, naïve hNPC alone do not have any significant functional effects in models of PD.…”

Section: Introductionmentioning

confidence: 99%

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Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

et al. 2005

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Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Growthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

et al. 2005

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“…Since transplanted NPCs (and especially in the form of spheres) integrate and survive in the adult brain better than mature cells (Svendsen et al, 1998;Pluchino et al, 2007), we grafted undifferentiated NPC spheres. The survival, distribution, and differentiation of transplanted cells labeled with PKH-26 were examined after completion of the behavioral tests.…”

Section: Transplantation and Characterization Of Il-1ratg Npcs In Vivomentioning

confidence: 99%

Intrahippocampal Transplantation of Transgenic Neural Precursor Cells Overexpressing Interleukin-1 Receptor Antagonist Blocks Chronic Isolation-Induced Impairment in Memory and Neurogenesis

Menachem-Zidon

Goshen

Kreisel

et al. 2007

Neuropsychopharmacol

130

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The proinflammatory cytokine interleukin-1 (IL-1) within the brain is critically involved in mediating the memory impairment induced by acute inflammatory challenges and psychological stress. However, the role of IL-1 in memory impairment and suppressed neurogenesis induced by chronic stress exposure has not been investigated before now. We report here that mice that were isolated for 4 weeks displayed a significant elevation in hippocampal IL-1b levels concomitantly with body weight loss, specific impairment in hippocampaldependent memory, and decreased hippocampal neurogenesis. To examine the causal role of IL-1 in these effects, we developed a novel approach for long-term delivery of IL-1 receptor antagonist (IL-1ra) into the brain, using transplantation of neural precursor cells (NPCs), obtained from neonatal mice with transgenic overexpression of IL-1ra (IL-1raTG) under the glial fibrillary acidic protein promoter. Four weeks following intrahippocampal transplantation of IL-1raTG NPCs labeled with PKH-26, the transplanted cells were incorporated within the dentate gyrus and expressed mainly astrocytic markers. IL-1ra levels were markedly elevated in the hippocampus, but not in other brain regions, by 10 days and for at least 4 weeks post-transplantation. Transplantation of IL-1raTG NPCs completely rescued the chronic isolation-induced body weight loss, memory impairment, and suppressed hippocampal neurogenesis, compared with isolated mice transplanted with WT cells or sham operated. The transplantation had no effect in group-housed mice. These findings elucidate the role of IL-1 in the pathophysiology of chronic isolation and suggest that transplantation of IL-1raTG NPCs may provide a useful therapeutic procedure for IL-1-mediated memory disturbances in chronic inflammatory and neurological conditions.

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Comparative Human and Rat “Neurosphere Assay” for Developmental Neurotoxicity Testing

et al. 2014

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The developing nervous system is highly vulnerable to the adverse effects of chemical agents. Currently, there is an increasing need for testing and regulating chemical compounds in general use and, due to the lack of available data, to identify those which are developmental neurotoxicants. In this context, alternative testing strategies are needed in order to allow fast and cost-efficient screening and to reduce the number of animal experiments usually required. In this unit we present an in vitro three-dimensional model for developmental neurotoxicity screening based on human and rat neural progenitor cells. This model enables the detection of disturbances in basic processes of brain development, such as proliferation, migration, differentiation and apoptosis, and allows the distinction of these specific disturbances from general cytotoxicity. Furthermore, the comparison of human and rat data provides useful insights into species differences for toxicodynamics of compounds contributing to human risk assessment of developmental neurotoxicants.

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A new method for the rapid and long term growth of human neural precursor cells

Cited by 552 publications

References 31 publications

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

Intrahippocampal Transplantation of Transgenic Neural Precursor Cells Overexpressing Interleukin-1 Receptor Antagonist Blocks Chronic Isolation-Induced Impairment in Memory and Neurogenesis

Comparative Human and Rat “Neurosphere Assay” for Developmental Neurotoxicity Testing

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