Establishment of an immortalized GABAergic neuronal progenitor cell line from embryonic ventral mesencephalon in the rat

Wang, Beibei; Zou, Xiaobao; Zhang, Haiyan; Duan, Deyi; Ju, Lin; Jiang, Xiaohua; Sun, Xuehua; Zhao, Chunli; Zhao, Huanying; Guo, Jin; Xu, Changlei; Gao, Erjing; Xu, Qian

doi:10.1016/j.brainres.2008.02.062

Cited by 10 publications

(17 citation statements)

References 51 publications

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“…Recently, other novel stem cells have emerged and been reported to have good prospects for neural restoration. These include iPSCs, the induced neural stem/progenitor cells (iNSCs) and a thermally controlled immortalized γ‐aminobutyric acid (GABA)ergic neuronal progenitor cell line (RMNE6) . All types were found to be, to a certain extent, capable of overcoming the limitations and challenges in the practical application of stem cells.…”

Section: Introductionmentioning

confidence: 99%

Comparison of intracerebral transplantation effects of different stem cells on rodent stroke models

et al. 2015

Cell Biochemistry & Function

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In the present study, induced pluripotent stem cells (iPSCs), induced neural stem cells (iNSCs), mesenchymal stem cells (MSCs) and an immortalized cell line (RMNE6), representing different characteristics of stem cells, were transplanted into normal and/or injured brain areas of rodent stroke models, and their effects were compared to select suitable stem cells for cell replacement stroke therapy. The rat and mice ischaemic models were constructed using the middle cerebral artery occlusion technique. Both electrocoagulation of the artery and the intraluminal filament technique were used. The behaviour changes and fates of grafted stem cells were determined mainly by behaviour testing and immunocytochemistry. Following iPSC transplantation into the corpora striata of normal mice, a tumour developed in the brain. The iNSCs survived well and migrated towards the injured area without differentiation. Although there was no tumourigenesis in the brain of normal or ischaemic mice after the iNSCs were transplanted in the cortices, the behaviour in ischaemic mice was not improved. Upon transplanting MSC and RMNE6 cells into ischaemic rat brains, results similar to iNSCs in mice were seen. However, transplantation of RMNE6 caused a brain tumour. Thus, tumourigenesis and indeterminate improvement of behaviour are challenging problems encountered in stem cell therapy for stroke, and the intrinsic characteristics of stem cells should be remodelled before transplantation. Copyright © 2015 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Comparison of intracerebral transplantation effects of different stem cells on rodent stroke models

et al. 2015

Cell Biochemistry & Function

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“…Conditionally immortalized progenitor cells have a consistent lineage that allows them to differentiate into a cell line with a specific phenotype. A number of GABAergic cell lines of striatal or mesencephalic origin that express GAD 67 and produce GABA in vitro have been generated and used for molecular studies of GABA cell regulation [11], [12], [13], [14], [15]. However, a GABAergic cell line derived from the hippocampus has not as yet been developed and will be of critical importance for in vitro modeling of GABA cell differentiation and functional regulation, as it relates to this region.…”

Section: Introductionmentioning

confidence: 99%

Induction of the GABA Cell Phenotype: An In Vitro Model for Studying Neurodevelopmental Disorders

Subburaju

Beneš

2012

PLoS ONE

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Recent studies of the hippocampus have suggested that a network of genes is associated with the regulation of the GAD67 (GAD1) expression and may play a role in γ-amino butyric acid (GABA) dysfunction in schizophrenia (SZ) and bipolar disorder (BD). To obtain a more detailed understanding of how GAD67 regulation may result in GABAergic dysfunction, we have developed an in vitro model in which GABA cells are differentiated from the hippocampal precursor cell line, HiB5. Growth factors, such as PDGF, and BDNF, regulate the GABA phenotype by inducing the expression of GAD67 and stimulating the growth of cellular processes, many with growth cones that form appositions with the cell bodies and processes of other GAD67-positive cells. These changes are associated with increased expression of acetylated tubulin, microtubule-associated protein 2 (MAP2) and the post-synaptic density protein 95 (PSD95). The addition of BDNF, together with PDGF, increases the levels of mRNA and protein for GAD67, as well as the high affinity GABA uptake protein, GAT1. These changes are associated with increased concentrations of GABA in the cytoplasm of “differentiated” HiB5 neurons. In the presence of Ca2+ and K+, newly synthesized GABA is released extracellularly. When the HiB5 cells appear to be fully differentiated, they also express GAD65, parvalbumin and calbindin, and GluR subtypes as well as HDAC1, DAXX, PAX5, Runx2, associated with GAD67 regulation. Overall, these results suggest that the HiB5 cells can differentiate into functionally mature GABA neurons in the presence of gene products that are associated with GAD67 regulation in the adult hippocampus.

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“…Cells immortalized with the tsSV40T oncogene proliferate under the permissive temperature of 33uC, whereas they differentiate at the non-permissive temperature of 39uC (Chou, 1989;Jat and Sharp, 1989). In fact, several tsSV40T-immortalized neuronal cell lines have been shown to retain their capacity to differentiate when the immortalizing oncogene has been inactivated (Eves et al, 1992;Whittemore and White, 1993;White et al, 1994;Son et al, 1999;McManus et al, 1999;Barber et al, 2000;Matsushita et al, 2006;Wang et al, 2008;Barenco et al, 2009). In fact, several tsSV40T-immortalized neuronal cell lines have been shown to retain their capacity to differentiate when the immortalizing oncogene has been inactivated (Eves et al, 1992;Whittemore and White, 1993;White et al, 1994;Son et al, 1999;McManus et al, 1999;Barber et al, 2000;Matsushita et al, 2006;Wang et al, 2008;Barenco et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Establishment and characterization of a noradrenergic adrenal chromaffin cell line, tsAM5NE, immortalized with the temperature-sensitive SV40 T-antigen

et al. 2011

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We established a clonal adrenal medullary cell line, named tsAM5NE, from transgenic mice harbouring the temperature-sensitive Simian virus 40 large T-antigen gene, under the control of the tyrosine hydroxylase promoter. tsAM5NE cells conditionally grew at a permissive temperature of 33°C and exhibited the noradrenergic chromaffin cell phenotype. To understand the characteristics of tsAM5NE cells, we first examined the responsiveness of the cells to ligands of the GDNF (glial cell line-derived neurotrophic factor) family. tsAM5NE cells proliferated at the permissive temperature of 33°C in response to either GDNF or neurturin, but not artemin or persephin. At the non-permissive temperature of 39°C, GDNF or neurturin caused tsAM5NE cells to differentiate into neuron-like cells; however, the differentiated cells died in a time-dependent manner. Interestingly, LIF (leukaemia inhibitory factor) did not affect the GDNF-mediated cell proliferation at 33°C, but promoted the survival and differentiation of GDNF-treated cells at 39°C. In the presence of GDNF plus LIF, the morphological change induced by the temperature shift was associated with up-regulated expression of neuronal markers, indicating that the cells had indeed undergone neuronal differentiation. Thus, we demonstrated that tsAM5NE cells had the capacity to terminally differentiate into neuron-like cells in response to GDNF plus LIF when the oncogene was inactivated by the temperature shift. Thus, this cell line provides a useful model system for studying the mechanisms regulating neuronal differentiation.

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Establishment of an immortalized GABAergic neuronal progenitor cell line from embryonic ventral mesencephalon in the rat

Cited by 10 publications

References 51 publications

Comparison of intracerebral transplantation effects of different stem cells on rodent stroke models

Comparison of intracerebral transplantation effects of different stem cells on rodent stroke models

Induction of the GABA Cell Phenotype: An In Vitro Model for Studying Neurodevelopmental Disorders

Establishment and characterization of a noradrenergic adrenal chromaffin cell line, tsAM5NE, immortalized with the temperature-sensitive SV40 T-antigen

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