Development of Neuronal Networks from Single Stem Cells Harvested from the Adult Human Brain

Moe, Morten C.; Westerlund, Ulf; Varghese, Mercy; Berg-Johnsen, Jon; Svensson, Mikael; Langmoen, Iver A.

doi:10.1227/01.neu.0000159881.09663.6d

Cited by 47 publications

(52 citation statements)

References 163 publications

(167 reference statements)

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“…This variation indicated that the neuron-like cells had a wide range of different sizes and=or electrical characteristics that could reflect differences in their developmental stages or the types of neurons being generated. The passive membrane properties of the neuron-like cells were similar to previously published data for neurons differentiated from human and rodent embryonic stem cells [27,29], human and rodent NSCs [28,[30][31][32], and rodent MeSCs [33]. Although the passive properties revealed that the NSC-like cells might have differentiated into a diverse population of neuron-like cells, it did not indicate anything about their functional characteristics.…”

Section: Membrane Properties Of Neuron-like Cells Differentiated Fromsupporting

confidence: 81%

“…Previous calcium imaging studies have show that cells differentiated from adult MeSCs, adult NSCs, and embryonic stem cells respond to depolarization with KCl or the application of the neurotransmitter l-glutamate with an increase in cytoplasmic Ca 2þ levels [27,31,38,55,56]. These transient changes in the Ca 2þ levels are important for regulating neuronal differentiation, transmitter selection, and axonal targeting in immature neurons [57,58].…”

Section: Development Of Kcl and L-glutamate-induced Increases In Cytomentioning

confidence: 99%

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Membrane Properties of Neuron-Like Cells Generated from Adult Human Bone-Marrow-Derived Mesenchymal Stem Cells

Fox

Shen

et al. 2010

Stem Cells and Development

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Adult mesenchymal stem cells (MeSCs) isolated from human bone marrow are capable of generating neural stem cell (NSC)-like cells that can be subsequently differentiated into cells expressing molecular markers for neurons. Here we report that these neuron-like cells had functional properties similar to those of brain-derived neurons. Whole-cell patch-clamp recordings and calcium imaging experiments were performed on neuron-like cells differentiated from bone-marrow-derived NSC-like cells. The neuron-like cells were subjected to current pulses to determine if they were capable of generating depolarization-induced action potentials. We found that nearly all of the cells with neuron-like morphology exhibited active membrane properties in response to the depolarizing pulses. The most common response was a single spike-like event with an overshoot and brief afterhyperpolarization. Cells that did not generate overshooting spike-like events usually displayed rectifying current-voltage relationships. The prevalence of these active membrane properties in response to the depolarizing current pulses suggested that the human MeSCs (hMeSCs) were capable of converting to a neural lineage under defined culture conditions. The spike-like events were blocked by the voltage-gated sodium channel inhibitor lidocaine, but unaffected by another sodium channel inhibitor tetrodotoxin (TTX). In calcium imaging experiments, the neuron-like cells responded to potassium chloride depolarization and l-glutamate application with increases in the cytoplasmic calcium levels. Thus, the neuron-like cells appeared to express TTX-resistant voltage-gated sodium channels, voltage-gated calcium channels, and functional l-glutamate receptors. These results demonstrate that hMeSCs were capable of generating cells with characteristics typical of functional neurons that may prove useful for neuroreplacement therapies.

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Section: Membrane Properties Of Neuron-like Cells Differentiated Fromsupporting

confidence: 81%

Section: Development Of Kcl and L-glutamate-induced Increases In Cytomentioning

confidence: 99%

Membrane Properties of Neuron-Like Cells Generated from Adult Human Bone-Marrow-Derived Mesenchymal Stem Cells

Fox

Shen

et al. 2010

Stem Cells and Development

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“…NPCs hold the promise of repairing and finally curing degenerative disorders, such as Parkinson's disease or amyotrophic lateral sclerosis, stroke, or head trauma [1,2]. NPCs can be isolated from human fetal brain tissue [3,4] as well as from several regions of the adult human brain such as cortex, hippocampus, or subventricular zone (SVZ) of the lateral ventricles [5][6][7][8][9][10][11][12]. These human NPCs are typically expanded as neurosphere cultures and differentiate exclusively in neural cell types using specific culture conditions.…”

Section: Introductionmentioning

confidence: 99%

Transcription Profiling of Adult and Fetal Human Neuroprogenitors Identifies Divergent Paths to Maintain the Neuroprogenitor Cell State

et al. 2007

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Global gene expression profiling was performed using RNA from adult human hippocampus-derived neuroprogenitor cells (NPCs) and multipotent frontal cortical fetal NPCs compared with adult human mesenchymal stem cells (hMSCs) as a multipotent adult stem cell control, and adult human hippocampal tissue, to define a gene expression pattern that is specific for human NPCs. The results were compared with data from various databases. Hierarchical cluster analysis of all neuroectodermal cell/tissue types revealed a strong relationship of adult hippocampal NPCs with various white matter tissues, whereas fetal NPCs strongly correlate with fetal brain tissue. However, adult and fetal NPCs share the expression of a variety of genes known to be related to signal transduction, cell metabolism and neuroectodermal tissue. In contrast, adult NPCs and hMSCs overlap in the expression of genes mainly involved in extracellular matrix biology. We present for the first time a detailed transcriptome analysis of human adult NPCs suggesting a relationship between hippocampal NPCs and white matter-derived precursor cells. We further provide a framework for standardized comparative gene expression analysis of human brain-derived NPCs with other stem cell populations or differentiated tissues.

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“…The isolation of these cells could lead to a future source of autologous transplants for neurodegenerative diseases, as well as to the storage for future research for basic science studies of NSCs. However, only few studies have described the isolation of NSCs from human brain in vivo [7][8][9] , and no such study has been performed in Brazil.…”

mentioning

confidence: 99%

Isolation of neurosphere-like bodies from an adult patient with refractory temporal lobe epilepsy

Azevedo-Pereira

Medei

Mendez-Otero

et al. 2010

Arq. Neuro-Psiquiatr.

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Development of Neuronal Networks from Single Stem Cells Harvested from the Adult Human Brain

Cited by 47 publications

References 163 publications

Membrane Properties of Neuron-Like Cells Generated from Adult Human Bone-Marrow-Derived Mesenchymal Stem Cells

Membrane Properties of Neuron-Like Cells Generated from Adult Human Bone-Marrow-Derived Mesenchymal Stem Cells

Transcription Profiling of Adult and Fetal Human Neuroprogenitors Identifies Divergent Paths to Maintain the Neuroprogenitor Cell State

Isolation of neurosphere-like bodies from an adult patient with refractory temporal lobe epilepsy

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