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Neurosphere

About: Neurosphere is a research topic. Over the lifetime, 5145 publications have been published within this topic receiving 321088 citations.


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Journal ArticleDOI
TL;DR: The results suggest that EGF, IGF‐1, FGF‐2, and SCF are important cytokines for stimulating the proliferation of MDSC, and illustrates the importance of monitoring several parameters of cell growth, such as DT and dividing fraction, following stimulation with growth factors.
Abstract: Stem cell expansion and proliferation are important for cell transplantation and stem cell-mediated applications. While we have demonstrated that muscle stem cells can be obtained from adult skeletal muscle tissue, these cells represent only a small percentage of the muscle-derived cells and require in vitro expansion for successful stem cell-mediated therapies. In this study, we have examined the potential of several cytokines to stimulate stem cell growth by combining a non-exponential mathematical model with a unique cell culture system. The growth kinetics of two populations of muscle stem cells were characterized in culture medium supplemented with epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), FLT-3 ligand, hepatocyte growth factor, or stem cell factor (SCF). The division time (DT) and fraction of mitotically active cells were investigated as key parameters to further understand the mechanism of the expansion of the stem cell populations. Our results show that expansion of the freshly isolated, muscle-derived stem cells (MDSC) occurred by recruiting cells into the cell cycle in the presence of EGF, IGF-1, and SCF. However, expansion of the cultured stem cell clone, MC13, is attributed to a reduction of the length of the cell cycle in the presence of FGF-2, EGF, IGF-1, and SCF. Both MDSC and MC13 growth were inhibited in the presence of FLT-3 ligand by increasing the length of the cell cycle. Our results suggest that EGF, IGF-1, FGF-2, and SCF are important cytokines for stimulating the proliferation of MDSC. In addition, this study illustrates that expansion of stem cells occurs through different mechanisms, which consequently demonstrates the importance of monitoring several parameters of cell growth, such as DT and dividing fraction, following stimulation with growth factors.

112 citations

Journal ArticleDOI
TL;DR: The retinal and ciliary epithelium stem cells/progenitors appear to share similar signaling pathways that are emerging as important regulators of stem cells in general, yet, they are different in certain respects, such as in the potential to self-renew.

111 citations

Journal ArticleDOI
TL;DR: It is shown that mammalian target of rapamycin (mTOR) signaling is pivotal in determining proliferation versus quiescence in the adult forebrain neural stem cell (NSC) niche, and mTORC1 activity and progenitor proliferation decline within the quiescent NSC niche of the aging brain.
Abstract: Adult forebrain neurogenesis is dynamically regulated. Multiple families of niche-derived cues have been implicated in this regulation, but the precise roles of key intracellular signaling pathways remain vaguely defined. Here, we show that mammalian target of rapamycin (mTOR) signaling is pivotal in determining proliferation versus quiescence in the adult forebrain neural stem cell (NSC) niche. Within this niche, mTOR complex-1 (mTORC1) activation displays stage specificity, occurring in transiently amplifying (TA) progenitor cells but not in GFAP+ stem cells. Inhibiting mTORC1 depletes the TA progenitor pool in vivo and suppresses epidermal growth factor (EGF)-induced proliferation within neurosphere cultures. Interestingly, mTORC1 inhibition induces a quiescence-like phenotype that is reversible. Likewise, mTORC1 activity and progenitor proliferation decline within the quiescent NSC niche of the aging brain, while EGF administration reactivates the quiescent niche in an mTORC1-dependent manner. These findings establish fundamental links between mTOR signaling, proliferation, and aging-associated quiescence in the adult forebrain NSC niche.

111 citations

Journal ArticleDOI
01 Sep 2005-Brain
TL;DR: The findings demonstrate that at an early stage, MPCs often stain with neuronal markers without possessing any functional neuronal properties, and the adult human brain thus harbours MPCs, which have the ability to develop into neurons and in doing this follow characteristic steps of neurogenesis as seen in the developing brain.
Abstract: It was long held as an axiom that new neurons are not produced in the adult human brain. More recent studies have identified multipotent cells whose progeny express glial or neuronal markers. This discovery may lead to new therapeutic strategies for CNS disorders, either by stimulating neurogenesis in vivo or by transplanting multipotent progenitor cells (MPCs) that have been propagated and differentiated in vitro. The clinical application of such approaches will be limited by the ability of these cells to develop into functional neurons. To facilitate an understanding of mechanisms regulating neurogenesis in the adult human brain, we characterized the developmental processes MPCs go through when progressing to a neuron. Human tissue was harvested during temporal lobe resections because of epilepsy, and cells were cultured as neurospheres. Our findings demonstrate that at an early stage, these cells often stain with neuronal markers without possessing any functional neuronal properties. Over a period of 4 weeks in culture, cells go through characteristic steps of morphological and electrophysiological development towards functional neurons; they develop a polarized appearance with multiple dendrites, whereas the membrane potential becomes more negative and the input resistance decreases [from -48 +/- 10 mV/557 +/- 85 MOmega (n = 15) between days 7 and 11 to -59 +/- 9 mV/380 +/- 79 MOmega (n = 9) between days 25 and 38, respectively]. Active membrane properties were first observed on day 7 and consisted of a voltage-gated K+-current. Later in the second week the cells developed voltage-gated Ca2+-channels and fired small Ca2+-driven action potentials. Immature Na+-driven action potentials developed from the beginning of the third week, and by the end of the fourth week the cells fired repetitive action potentials with a completely mature waveform generated by the combined action of the voltage-gated ionic channels INa, IA and IK. After 4 weeks, the newly formed neurons also communicated by the use of GABAergic and glutamatergic synapses. The adult human brain thus harbours MPCs, which have the ability to develop into neurons and in doing this follow characteristic steps of neurogenesis as seen in the developing brain.

111 citations

Journal ArticleDOI
Akiko Yokoyama1, Lihua Yang1, Suzuka Itoh1, Kohji Mori1, Junya Tanaka1 
01 Jan 2004-Glia
TL;DR: A novel role of microglia as multipotential stem cells to give rise to neurons, astrocytes, or oligodendrocyte precursor cells is suggested.
Abstract: Microglia are considered the only cell population of mesodermal origin in the brain, although their role is not fully understood. The present study demonstrated that rat primary microglial cells expressed nestin, A2B5, and O4 antigens, which are markers for oligodendrocyte precursor cells. Based on these findings, we investigated whether microglial cells generated neurons or macroglial cells. Purified microglial cells were cultured in the presence of 10% fetal bovine serum for 3 days, followed by culture in the presence of 70% serum for 2 days. During the two-step culture, microglial cells became highly proliferative and strongly expressed inhibitor of DNA binding (Id) genes, indicative of dedifferentiation of the cells. The dedifferentiated cells also expressed transcription factors that promote differentiation into neurons or macroglial cells. When the dedifferentiated cells were transferred into serum-free medium on poly-L-lysine-coated substrate, a substantial number of the cells rapidly turned into long process-bearing cells, which expressed microtubule-associated protein 2, synapsin I, neurofilament proteins, glial fibrillary acidic protein, or galactocerebroside. When microglial cells were fluorescently labeled through acetylated low-density lipoprotein (LDL) receptors or by a phagocytosis-dependent mechanism, fluorescence-bearing neurons, astrocytes, or oligodendrocytes were observed. Neurospheres, aggregates of neural stem cells, expressed Musashi 1 and epidermal growth factor receptor, but the microglia-derived cells did not. These results suggest a novel role of microglia as multipotential stem cells to give rise to neurons, astrocytes, or oligodendrocytes.

111 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
2023131
2022140
2021121
2020121
2019124