Regional Specification of Neurosphere Cultures Derived from Subregions of the Embryonic Telencephalon

Parmar, Malin; Skogh, Charlotta; Björklund, Anders; Campbell, Kenneth

doi:10.1006/mcne.2002.1204

Cited by 95 publications

(66 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One of the major differences between LGE cells expanded as monolayer or neurosphere cultures is that the Gsh2-expressing progenitors are maintained only in the neurosphere cultures (Parmar et al, 2002;Skogh et al, 2003). To examine whether the potential for striatal neuron differentiation in neurosphereexpanded cells depends on the presence of these Gsh2-expressing progenitors, we made use of genetically modified mice lacking Gsh2 (Szucsik et al, 1997).…”

Section: The Observed Striatal Neuron Differentiation In Neurosphereementioning

confidence: 99%

“…When neural precursor cells are isolated from embryonic or adult brain and expanded in vitro under mitogen stimulation, the expanded cells maintain many aspects of their regional identity (Zappone et al, 2000;Yamamoto et al, 2001;Hitoshi et al, 2002;Parmar et al, 2002). However, we have previously shown that the differentiation potential of growth factor-expanded LGE cells are compromised: the expanded LGE cells generate neurons with characteristics of olfactory bulb interneurons but not striatal projection neurons under standard in vitro differentiation conditions (Skogh et al, 2001(Skogh et al, , 2003Parmar et al, 2002).…”

Section: Introductionmentioning

confidence: 95%

“…However, we have previously shown that the differentiation potential of growth factor-expanded LGE cells are compromised: the expanded LGE cells generate neurons with characteristics of olfactory bulb interneurons but not striatal projection neurons under standard in vitro differentiation conditions (Skogh et al, 2001(Skogh et al, , 2003Parmar et al, 2002). This might suggest that the progenitors of striatal projection neurons are not expandable in culture.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Striatal Neuron Differentiation from Neurosphere-Expanded Progenitors Depends onGsh2Expression

Jensen¹,

Björklund²,

Parmar³

2004

J. Neurosci.

View full text Add to dashboard Cite

Neural stem and progenitor cells from the embryonic forebrain can be expanded under growth factor stimulation in vitro, either as free-floating aggregates called neurospheres or as attached monolayer cultures. We have previously shown that despite the maintenance of important regulatory genes such as Gsh2, in vitro expansion of cells from the lateral ganglion eminence (LGE) restricts their differentiation potential. Specifically, their ability to differentiate into striatal projection neurons is compromised. It is not clear whether this restriction is caused by loss of progenitors with the ability to generate striatal projection neurons or whether the restricted differentiation potential is caused by factors lacking during in vitro differentiation. To address this, we have set up an in vitro system, in which expanded LGE-derived cells are differentiated in coculture with primary cells isolated from different regions of the embryonic brain. We provide evidence that the primary cells supply the expanded cells with contact-mediated region-specific developmental cues. Neurosphereexpanded LGE progenitors can, when presented with these cues, differentiate into neurons with characteristics of striatal projection neurons. Furthermore, we show that the ability of the expanded LGE cells to respond to the developmental cues presented by the primary cells depends on the maintained expression of Gsh2 in the expanded cells.

show abstract

Section: The Observed Striatal Neuron Differentiation In Neurosphereementioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Striatal Neuron Differentiation from Neurosphere-Expanded Progenitors Depends onGsh2Expression

Jensen¹,

Björklund²,

Parmar³

2004

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In this study, we performed multiple transplantation experiments using NSC are traditionally isolated and cultured from embryonic (13, 27,53) or adult brain tissue (11,31,(43)(44)(45), well-defined NSC cultures and aim to provide a detailed report regarding the clinical relevance of IV administraand proliferate in suspension culture as spherical aggregates, designated as neurospheres. These neurospheres tion of allogeneic NSCs for treatment of murine EAE in view of the potential application of NSCs for treatment consist of multipotent stem cells that are normally present in very small numbers, and progenitor cells that are of human MS. more restricted in proliferation and differentiation poten-MATERIALS AND METHODS tial (22,36). Novel culture protocols have recently been Animals described in order to expand large numbers of selfrenewable uniform populations of adherently growing Homozygous ROSA26-L-S-L-Luciferase transgenic mice (49) (FVB background) were obtained from JackNSCs from embryonic stem cells and embryonic brain tissue (12,19,40).…”

Section: Introductionmentioning

confidence: 99%

Clinical Potential of Intravenous Neural Stem Cell Delivery for Treatment of Neuroinflammatory Disease in Mice?

et al. 2011

View full text Add to dashboard Cite

While neural stem cells (NSCs) are widely expected to become a therapeutic agent for treatment of severe injuries to the central nervous system (CNS), currently there are only few detailed preclinical studies linking cell fate with experimental outcome. In this study, we aimed to validate whether IV administration of allogeneic NSC can improve experimental autoimmune encephalomyelitis (EAE), a well-established animal model for human multiple sclerosis (MS). For this, we cultured adherently growing luciferase-expressing NSCs (NSC-Luc), which displayed a uniform morphology and expression profile of membrane and intracellular markers, and which displayed an in vitro differentiation potential into neurons and astrocytes. Following labeling with green fluorescent micron-sized iron oxide particles (f-MPIO-labeled NSC-Luc) or lentiviral transduction with the enhanced green fluorescent protein (eGFP) reporter gene (NSC-Luc/eGFP), cell implantation experiments demonstrated the intrinsic survival capacity of adherently cultured NSC in the CNS of syngeneic mice, as analyzed by real-time bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and histological analysis. Next, EAE was induced in C57BL/6 mice followed by IV administration of NSC-Luc/eGFP at day 7 postinduction with or without daily immunosuppressive therapy (cyclosporine A, CsA). During a follow-up period of 20 days, the observed clinical benefit could be attributed solely to CsA treatment. In addition, histological analysis demonstrated the absence of NSC-Luc/eGFP at sites of neuroinflammation. In order to investigate the absence of therapeutic potential, BLI biodistribution analysis of IV-administered NSC-Luc/eGFP revealed cell retention in lung capillaries as soon as 1-min postinjection, resulting in massive inflammation and apoptosis in lung tissue. In summary, we conclude that IV administration of NSCs currently has limited or no therapeutic potential for neuroinflammatory disease in mice, and presumably also for human MS. However, given the fact that grafted NSCs have an intrinsic survival capacity in the CNS, their therapeutic exploitation should be further investigated, and-in contrast to several other reports-will most likely be highly complex.

show abstract

“…Thus, neural precursor cells from different levels of the neuraxis express different molecular markers, some of which are retained even during mitogenic expansion and passaging. 32,44,75,76 Regional specification exists even within brain regions. 24 For example, differentiation of the various cell types of the telencephalon occurs due to variations in the expression of transcription factors by subpopulations of precursor cells within this structure.…”

Section: Influence Of the Region Of Hnpc Originmentioning

confidence: 99%

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

Mukhida

Baghbaderani

Hong

et al. 2008

FOC

View full text Add to dashboard Cite

Object Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. Methods Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8–10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. Results The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. Conclusions Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.

show abstract

Regional Specification of Neurosphere Cultures Derived from Subregions of the Embryonic Telencephalon

Cited by 95 publications

References 66 publications

Striatal Neuron Differentiation from Neurosphere-Expanded Progenitors Depends onGsh2Expression

Striatal Neuron Differentiation from Neurosphere-Expanded Progenitors Depends onGsh2Expression

Clinical Potential of Intravenous Neural Stem Cell Delivery for Treatment of Neuroinflammatory Disease in Mice?

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

Contact Info

Product

Resources

About