Tumor Necrosis Factor-α Modulates Survival, Proliferation, and Neuronal Differentiation in Neonatal Subventricular Zone Cell Cultures

Bernardino, Liliana; Agasse, Fabienne; Silva, Bruno; Ferreira, Raquel; Grade, Sofia; Malva, João O.

doi:10.1634/stemcells.2007-0914

Cited by 189 publications

(167 citation statements)

References 69 publications

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“…[11][12][13][14] In hMSCs, TNF-a can act as a chemoattractant and stimulates MMP/TIMP-expression as previously reported by us. 20 Here, we demonstrate that prolonged cultivation of hMSCs in the presence of TNF-a (50 ng/ml) evokes a remarkable change in cell morphology, which was similar to the characteristic star-shaped appearance of astrocytic glial cells present in brain and spinal cord.…”

Section: Discussionsupporting

confidence: 64%

“…In contrast, similar dosages of TNF-a are reported to induce apoptotic cell death in neural stem/progenitor cells. 13 Lower concentrations of TNF-a, however, consistently stimulated the proliferation of both hMSCs and neural stem/ progenitor cells. These findings indicate that the cellular implications initiated by TNF-a are highly dose-dependent and vary between different cell types.…”

Section: Discussionmentioning

confidence: 97%

“…10 In the brain, TNF-a was shown to influence growth, survival, and neuronal differentiation of neural stem/progenitor cells, which is mediated via signaling through its cellular receptor tumor necrosis factor receptor (TNF-R)1, thereby modulating tissue regeneration after stroke, inflammation, and status epilepticus. [11][12][13][14] At the molecular level, TNF-a-induced effects are mediated via binding to TNF-R1 and/or TNF-R2 with subsequent intracellular signaling through several different pathways including that of NF-kB and the mitogen-activated protein kinases (MAPKs). 9 The three major MAPK cascades comprise ERK1/2 (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38.…”

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confidence: 99%

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TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

et al. 2010

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Bone marrow-derived human mesenchymal stem cells (hMSCs) have become valuable candidates for cell-based therapeutical applications including neuroregenerative and anti-tumor strategies. Yet, the molecular mechanisms that control hMSC transdifferentiation to neural cells and hMSC tropism toward glioma remain unclear. Here, we demonstrate that hMSCs incubated with 50 ng/ml tumor necrosis factor alpha (TNF-a) acquired astroglial cell morphology without affecting proliferation, which was increased at 5 ng/ml. TNF-a (50 ng/ml) upregulated expression of numerous genes important for neural cell growth and function including LIF (leukemia inhibitory factor), BMP2 (bone morphogenetic protein 2), SOX2 (SRY box 2), and GFAP (glial fibrillary acidic protein), whereas NES (human nestin) transcription ceased suggesting a premature neural phenotype in TNF-adifferentiated hMSCs. Studies on intracellular mitogen-activated protein kinase (MAPK) signaling revealed that inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity abolished the TNF-a-mediated regulation of neural genes in hMSCs. In addition, TNF-a significantly enhanced expression of the chemokine receptor CXCR4 (CXC motive chemokine receptor 4), which facilitated the chemotactic invasiveness of hMSCs toward stromal cell-derived factor 1 (SDF-1) alpha. TNF-a-pretreated hMSCs not only exhibited an increased ability to infiltrate glioma cell spheroids dependent on matrix metalloproteinase activity in vitro, but they also showed a potentiated tropism toward intracranial malignant gliomas in an in vivo mouse model. Taken together, our results provide evidence that culture-expansion of hMSCs in the presence of TNF-a triggers neural gene expression and functional capacities, which could improve the use of hMSCs in the treatment of neurological disorders including malignant gliomas.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

et al. 2010

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“…In these conditions, SVZ cells grow in suspension and generate neurospheres that are rich in neural and progenitor stem cells at distinct stages of differentiation and with proliferative and selfrenewing abilities, as previously shown by us [7,24,[27][28][29][30]. Five to six-day-old neurospheres were seeded onto 0.1 mg/mL poly-D-lysine-(PDL; Sigma-Aldrich Co. Zeiss, Jena, Germany).…”

Section: Svz Cell Cultures and Experimental Treatmentsmentioning

confidence: 99%

MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

Saraiva

Paiva

Santos

et al. 2016

Journal of Controlled Release

139

116

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Modulation of the subventricular zone (SVZ) neurogenic niche can enhance brain repair in several disorders including Parkinson's disease (PD). Herein, we used biocompatible and traceable polymeric nanoparticles (NPs) containing perfluoro-1,5-crown ether (PFCE) and coated with protamine sulfate to complex microRNA-124 (miR-124), a neuronal fate determinant. The ability of NPs to efficiently deliver miR-124 and prompt SVZ neurogenesis and brain repair in PD was evaluated. In vitro, miR-124 NPs were efficiently internalized by neural stem/progenitors cells and neuroblasts and promoted their neuronal commitment and maturation. The expression of Sox9 and Jagged1, two miR-124 targets and stemness-related genes, were also decreased upon miR-124 NP treatment. In vivo, the intracerebral administration of miR-124 NPs increased the number of migrating neuroblasts that reached the granule cell layer of the olfactory bulb, both in healthy and in a 6-hydroxydopamine (6-OHDA) mouse model for PD.MiR-124 NPs were also able to induce migration of neurons into the lesioned striatum of 6-OHDA-treated mice. Most importantly, miR-124 NPs proved to ameliorate motor symptoms of 6-OHDA mice, monitored by the apomorphine-induced rotation test.Altogether, we provide clear evidences to support the use of miR-124 NPs as a new therapeutic approach to boost endogenous brain repair mechanisms in a setting of neurodegeneration.

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“…Indeed, KCl-induced depolarization and consequent [Ca 2+ ] i rise is typical of excitable neuronal cell lineage, whereas histamine triggers a response in immature cells. This method has unveil the pro-neurogenic effects of NPY and 5 TNF in mice SVZ cultures [9,10]. Here, we hypothesized whether thrombin can be similarly used as a specific stimulus for SVZ-derived oligodendrocytes.…”

Section: Introductionmentioning

confidence: 99%

Functional Identification of Neural Stem Cell–Derived Oligodendrocytes by Means of Calcium Transients Elicited by Thrombin

Grade

Agasse

Bernardino

et al. 2010

Rejuvenation Research

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In this work, we questioned whether SVZ-derived oligodendrocytes could be functionally discriminated on the basis of intracellular calcium levels ( Thrombin-induced calcium increase in oligodendrocytes is mediated by protease-activated receptor-1 (PAR-1) activation and downstream signaling through G q/11 and phospholipase C (PLC), resulting in calcium recruitment from intracellular compartments.This method allows the analysis of functional properties of oligodendrocytes in living SVZ cultures, which is of major interest for the development of effective grafting strategies in the demyelinated brain. Additionally, it opens new perspectives for the search of new prooligodendrogenic factors to be used prior grafting.

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Tumor Necrosis Factor-α Modulates Survival, Proliferation, and Neuronal Differentiation in Neonatal Subventricular Zone Cell Cultures

Cited by 189 publications

References 69 publications

TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

Functional Identification of Neural Stem Cell–Derived Oligodendrocytes by Means of Calcium Transients Elicited by Thrombin

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