Neurogenesis in adult human

Murrell, Wayne; Bushell, Gillian Robin; Livesey, J; McGrath, John J.; MacDonald, Kelli P. A.; Bates, Paul Raymond; Mackay‐Sim, Alan

doi:10.1097/00001756-199604260-00019

Cited by 86 publications

(59 citation statements)

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“…Human olfactory sensory neurons are continually regenerated throughout life (Murrell et al, 1996) from stem or progenitor cells in the olfactory epithelium (Chen et al, 2004;Leung et al, 2007). Olfactory neuroblasts (Wolozin et al, 1992b) and neurospheres (Roisen et al, 2001;Murrell et al, 2005) can be grown from the human olfactory mucosa.…”

Section: Technical Considerationsmentioning

confidence: 99%

“…Olfactory cell suspensions were generated by digestion with dispase II (Boehringer; 2.4 units/ml, 45 minutes, 37°C) and collagenase H (Sigma; 0.25 mg/ml, 10 minutes, 37°C) accompanied by mechanical trituration, as described previously (Murrell et al, 1996;Murrell et al, 2005). The primary cultures were grown for 3 days in DMEM/F12 supplemented with 10% FBS before passaging into flasks (Nunclon) pretreated with 1 g/cm 2 poly-L-lysine (Sigma, P6282) and culturing in DMEM/F12 containing EGF (50 ng/ml, Sigma) and FGF2 (25 ng/ml, Sigma).…”

Section: Cell Culturementioning

confidence: 99%

See 1 more Smart Citation

Disease-specific, neurosphere-derived cells as models for brain disorders

Matigian

Abrahamsen

Sutharsan

et al. 2010

Disease Models &Amp; Mechanisms

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181

237

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SUMMARYThere is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.

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Section: Technical Considerationsmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Disease-specific, neurosphere-derived cells as models for brain disorders

Matigian

Abrahamsen

Sutharsan

et al. 2010

Disease Models &Amp; Mechanisms

Self Cite

181

237

View full text Add to dashboard Cite

show abstract

“…Interestingly, cells that were cultured in the presence of FGF2 (in explant or clonal cultures) very rarely developed into neurons when cloned. Although FGF2 had previously been shown to promote neurogenesis in the adult striatal precursors [12] and adult olfactory epithelial cells [26,27], it has been shown by several groups, including our own, that FGF2 inhibits neuronal stem cell differentiation, although this appears to depend on FGF2 concentration [5,20,28,29]. Surprisingly, the culture condition that promoted the greatest frequency of clones containing neurons was in basal medium without additional growth factors.…”

Section: Discussionmentioning

confidence: 72%

Precursor Cells in the Subventricular Zone of the Adult Mouse Are Actively Inhibited from Differentiating into Neurons

Dutton

Bartlett²

2000

Dev Neurosci

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The adult mouse subventricular zone (SVZ) contains precursor cells capable of generating new neurons which populate the olfactory bulb. The SVZ precursors, however, appear to be restricted in their capacity to generate neurons in other regions of the brain indicating a tight regulation of their differentiation. We demonstrate in vitro that explants of SVZ are unable to generate neurons from dividing precursors, even though precursors are present and dividing within explant cultures. However, when plated as single cells in fibroblast growth factor-1 or with no growth factor, approximately 1% of harvested cells gave rise to clones containing neurons and astrocytes, indicating that bipotential precursors were present in the explants. Inhibitory effects of cell density were more directly shown by plating freshly isolated SVZ cells, or explant-derived SVZ cells, at increasing cell density. The frequency of neuron-containing wells was found to be greatly reduced at higher cell concentrations: >100 cells/well in the case of explant-derived cells and >500 cells in the case of freshly isolated cells. Thus, it appears that the precursor’s ability to generate neurons is actively inhibited by paracrine mechanisms which may be mediated by either cell-cell contact or by short-range factors.

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“…Subsequent studies confirmed the existence of this hippocampal neurogenesis in adulthood in several species including humans [91,92], using the new tool bromodeoxyuridine (BrdU), a thymidine analog that labels dividing cells in S-phase [93]. In the hippocampus, progenitor cells are located in the subgranular zone (SGZ) where they divide and a subset of the new cells survive, migrate into granule cell layer and differentiates into neurons.…”

Section: Neurogenesismentioning

confidence: 85%