• Title, Summary, Keyword: neural stem cells

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In Vitro Expansion of Homogeneous Neural Precursor Cells Derived from Human Embryonic Stem Cells

  • Na, Deuk-Chae;Kim, Se-Hee;Choi, Won-Ik;Hwang, Hyun-Jin;Han, In-Bo;Kim, Jae-Hwan;Park, Keun-Hong;Chung, Hyung-Min;Choi, Seong-Jun
    • Reproductive and Developmental Biology
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    • v.31 no.4
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    • pp.267-272
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    • 2007
  • Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and have the capacity to differentiate into various types of cells in the body. Hence, these cells may potentially be an indefinite source of cells for cell therapy in various degenerative diseases including neuronal disorders. For clinical applications of human ES cells, directed differentiation of these cells would be necessary. The objective of this study is to develop the culture condition for the expansion of neural precursor cells derived from human ES cells. Human ES cells were able to differentiate into neural precursor cells upon a stepwise culture condition. Neural precursor cells were propagated up to 5000-fold in cell numbers over 12-week period of culture and evaluated for their characteristics. Expressions of sox1 and pax6 transcripts were dramatically up-regulated along the differentiation stages by RT-PCR analysis. In contrast, expressions of oct4 and nanog transcripts were completely disappeared in neural precursor cells. Expressions of nestin, pax6 and sox1 were also confirmed in neural precursor cells by immunocytochemical analysis. Upon differentiation, the expanded neural precursor cells differentiated into neurons, astrocytes, and oligodendrocytes. In immunocytochemical analysis, expressions of type III ${\beta}$-tubulin and MAP2ab were observed Presence of astrocytes and oligodendrocytes were also confirmed by expressions of GFAP and O4, respectively. Results of this study demonstrate the feasibility of long-term expansion of human ES cell-derived neural precursor cells in vitro, which can be a potential source of the cells for the treatment of neurodegenerative disorders.

Neural Transcription Factors: from Embryos to Neural Stem Cells

  • Lee, Hyun-Kyung;Lee, Hyun-Shik;Moody, Sally A.
    • Molecules and Cells
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    • v.37 no.10
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    • pp.705-712
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    • 2014
  • The early steps of neural development in the vertebrate embryo are regulated by sets of transcription factors that control the induction of proliferative, pluripotent neural precursors, the expansion of neural plate stem cells, and their transition to differentiating neural progenitors. These early events are critical for producing a pool of multipotent cells capable of giving rise to the multitude of neurons and glia that form the central nervous system. In this review we summarize findings from gain- and loss-of-function studies in embryos that detail the gene regulatory network responsible for these early events. We discuss whether this information is likely to be similar in mammalian embryonic and induced pluripotent stem cells that are cultured according to protocols designed to produce neurons. The similarities and differences between the embryo and stem cells may provide important guidance to stem cell protocols designed to create immature neural cells for therapeutic uses.

Monitoring the Differentiation and Migration Patterns of Neural Cells Derived from Human Embryonic Stem Cells Using a Microfluidic Culture System

  • Lee, Nayeon;Park, Jae Woo;Kim, Hyung Joon;Yeon, Ju Hun;Kwon, Jihye;Ko, Jung Jae;Oh, Seung-Hun;Kim, Hyun Sook;Kim, Aeri;Han, Baek Soo;Lee, Sang Chul;Jeon, Noo Li;Song, Jihwan
    • Molecules and Cells
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    • v.37 no.6
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    • pp.497-502
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    • 2014
  • Microfluidics can provide unique experimental tools to visualize the development of neural structures within a microscale device, which is followed by guidance of neurite growth in the axonal isolation compartment. We utilized microfluidics technology to monitor the differentiation and migration of neural cells derived from human embryonic stem cells (hESCs). We co-cultured hESCs with PA6 stromal cells, and isolated neural rosette-like structures, which subsequently formed neurospheres in suspension culture. Tuj1-positive neural cells, but not nestin-positive neural precursor cells (NPCs), were able to enter the microfluidics grooves (microchannels), suggesting that neural cell-migratory capacity was dependent upon neuronal differentiation stage. We also showed that bundles of axons formed and extended into the microchannels. Taken together, these results demonstrated that microfluidics technology can provide useful tools to study neurite outgrowth and axon guidance of neural cells, which are derived from human embryonic stem cells.

A New Mathematical Model for Optimum Production of Neural Stem Cells in Large-scale

  • Hossain, S.M. Zakir;Sultana, Nahid;Babar, S.M. Enayetul;Haki, G.D.
    • Molecular & Cellular Toxicology
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    • v.3 no.2
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    • pp.77-84
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    • 2007
  • Millions of individuals worldwide are currently afflicted with neurodegenerative disorders such as Parkinson's disease and multiple sclerosis which are caused by the death of specific types of specialized cells in the Central Nervous System (CNS). Recently, Neural Stem Cells (NSCs) are able to replace these dead cells with new functional cells, thereby providing a cure for devastating neural diseases. The clinical use of neural stem cells (NSCs) for the treatment of neurological diseases requires overcoming the scarcity of the initial in vivo NSC population. Thus, we developed a novel 3-dimentional cellular automata model for optimum production of neural stem cells and their derivatives in large scale to treat neurodegenerative disorder patients.

Efficient In Vitro Labeling Rabbit Bone Marrow-Derived Mesenchymal Stem Cells with SPIO and Differentiating into Neural-Like Cells

  • Zhang, Ruiping;Li, Jing;Li, Jianding;Xie, Jun
    • Molecules and Cells
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    • v.37 no.9
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    • pp.650-655
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    • 2014
  • Mesenchymal stem cells (MSCs) can differentiate into neural cells to treat nervous system diseases. Magnetic resonance is an ideal means for cell tracking through labeling cells with superparamagnetic iron oxide (SPIO). However, no studies have described the neural differentiation ability of SPIO-labeled MSCs, which is the foundation for cell therapy and cell tracking in vivo. Our results showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) labeled in vitro with SPIO can be induced into neural-like cells without affecting the viability and labeling efficiency. The cellular uptake of SPIO was maintained after labeled BM-MSCs differentiated into neural-like cells, which were the basis for transplanted cells that can be dynamically and non-invasively tracked in vivo by MRI. Moreover, the SPIO-labeled induced neural-like cells showed neural cell morphology and expressed related markers such as NSE, MAP-2. Furthermore, whole-cell patch clamp recording demonstrated that these neural-like cells exhibited electrophysiological properties of neurons. More importantly, there was no significant difference in the cellular viability and $[Ca^{2+}]_i$ between the induced labeled and unlabeled neural-like cells. In this study, we show for the first time that SPIO-labeled MSCs retained their differentiation capacity and could differentiate into neural-like cells with high cell viability and a good cellular state in vitro.

Differentiation of Dopaminergic Neurons from Mesenchymal-Like Stem Cells Derived from Human Umbilical Cord Vein

  • Kim, Ju-Ran;Lee, Jin-Ha;Jalin, Anjela Melinda;Lee, Chae-Yeon;Kang, Ah-Reum;Do, Byung-Rok;Kim, Hea-Kwon;Kam, Kyung-Yoon;Kang, Sung-Goo
    • Development and Reproduction
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    • v.13 no.3
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    • pp.173-181
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    • 2009
  • One of the most extensively studied populations of multipotent adult stem cells are mesenchymal stem cells (MSCs). MSCs derived from the human umbilical cord vein (HUC-MSCs) are morphologically and immunophenotypically similar to MSCs isolated from bone marrow. HUC-MSCs are multipotent stem cells, differ from hematopoietic stem cells and can be differentiated into neural cells. Since neural tissue has limited intrinsic capacity of repair after injury, the identification of alternate sources of neural stem cells has broad clinical potential. We isolated mesenchymal-like stem cells from the human umbilical cord vein, and studied transdifferentiation-promoting conditions in neural cells. Dopaminergic neuronal differentiation of HUC-MSCs was also studied. Neural differentiation was induced by adding bFGF, EGF, dimethyl sulfoxide (DMSO) and butylated hydroxyanisole (BHA) in N2 medium and N2 supplement. The immunoreactive cells for $\beta$-tubulin III, a neuron-specific marker, GFAP, an astrocyte marker, or Gal-C, an oligodendrocyte marker, were found. HUC-MSCs treated with bFGF, SHH and FGF8 were differentiated into dopaminergic neurons that were immunopositive for tyrosine hydroxylase (TH) antibody. HUC-MSCs treated with DMSO and BHA rapidly showed the morphology of multipolar neurons. Both immunocytochemistry and RT-PCR analysis indicated that the expression of a number of neural markers including NeuroD1, $\beta$-tubulin III, GFAP and nestin was markedly elevated during this acute differentiation. While the stem cell markers such as SCF, C-kit, and Stat-3 were not expressed after neural differentiation, we confirmed the differentiation of dopaminergic neurons by TH/$\beta$-tubulin III positive cells. In conclusion, HUC-MSCs can be differentiated into dopaminergic neurons and these findings suggest that HUC-MSCs are alternative cell source of therapeutic treatment for neurodegenerative diseases.

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Regulation of Neural Stem Cell Fate by Natural Products

  • Kim, Hyun-Jung
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.15-24
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    • 2019
  • Neural stem cells (NSCs) can proliferate and differentiate into multiple cell types that constitute the nervous system. NSCs can be derived from developing fetuses, embryonic stem cells, or induced pluripotent stem cells. NSCs provide a good platform to screen drugs for neurodegenerative diseases and also have potential applications in regenerative medicine. Natural products have long been used as compounds to develop new drugs. In this review, natural products that control NSC fate and induce their differentiation into neurons or glia are discussed. These phytochemicals enable promising advances to be made in the treatment of neurodegenerative diseases.

Cytolytic Activities of Taxol on Neural Stem Cells

  • Lee, In-Soo;Han, Hye-Eun;Lee, Hye-Young;Kim, Seung-U.;Kim, Tae-Ue
    • Biomedical Science Letters
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    • v.13 no.4
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    • pp.273-278
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    • 2007
  • Stem cells have been the subject of increasing scientific interest because of their utility in numerous biomedical applications. Stem cells are capable of renewing themselves; that is, they can be continuously cultured in an undifferentiated state, giving rise to more specialized cells of the human body. Therefore, stem cells are an important new tools for developing unique, in vitro model systems to test drugs and chemicals and a potential to predict or anticipate toxicity in humans. In the present study, in vitro cultured F3 immortalized human neural stem cell line and in vivo adult Sprague Dawley rats was used to evaluate the cytotoxicity of anticancer drug paclitaxel. In vitro apoptotic activity of paclitaxel was evaluated in F3 cell line by a MTT assay and DAPI test. The cell death was induced with the treatment of 20 nM paclitaxel and chromatin degradation was detected by DAPI staining, which was analyzed by fluorescent microscope. In vivo studies, we also observed nestin immunoreactivity on subventricular zone, which is stem cell rich region in the adult brain of the SD rat. Immunofluorescent staining result shows that pixel intensities of nestin were decreased in a dose dependent manner. These results suggest that paclitaxel is able to induce cytotoxic activity both in F3 neural stem cell line and neural stem cell in SD rat brain.

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In Vitro Neural Cell Differentiation Derived from Human Embryonic Stem Cells: I. Effect of Neurotrophic Factors on Neural Progenitor Cells

  • Kim Eun-Yeong;Jo Hyeon-Jeong;Choe Gyeong-Hui;An So-Yeon;Jeong Gil-Saeng;Park Se-Pil;Im Jin-Ho
    • Proceedings of the KSAR Conference
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    • pp.18-18
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    • 2002
  • This study was to investigate the effect of neurotrophic factors on neural cell differentiation in vitro derived from human embryonic stem (hES, MB03) cells. For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for 7 - 10 days, 20 ng/㎖ of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron cells, neural progenitor cells were cultured in ⅰ) N2 medium (without bFGF), ⅱ) N2 supplemented with brain derived neurotrophic factor (BDNF, 5ng/㎖) or ⅲ) N2 supplemented with platelet derived growth factor-bb (PDGF-bb, 20ng/㎖) for 2 weeks. (omitted)

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Differential Expression of TPX2 upon Differentiation of Human Embryonic Stem Cells

  • Noh, Hye-Min;Choi, Seong-Jun;Kim, Se-Hee;Kim, Kye-Seong;Kim, Jin-Kyeoung
    • Reproductive and Developmental Biology
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    • v.31 no.4
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    • pp.221-226
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    • 2007
  • Embryonic stem (ES) cells are known to have an infinite proliferation and pluripotency that are associated with complex processes. The objective of this study was to examine expression of genes differentially regulated during differentiation of human ES cells by suppression subtractive hybridization (SSH). Human ES cells were induced to differentiate into neural precursor cells via embryoid body. Neural precursor cells were isolated physically based on morphological criteria. Immunocytochemical analysis showed expression of pax6 in neural precursor cells, confirming that the isolated cells were neural precursor cells. Undifferentiated human ES cells and neural precursor cells were subject to the SSH. TPX2 (Targeting Protein for Xklp2 (Xenopus centrosomal kinesin-like protein 2)) was identified, cloned and analyzed during differentiation of human ES cells into neural lineages. Expression of TPX2 was gradually down-regulated in embryoid bodies and neural precursor cells relative to undifferentiated ES cells. Targeting Protein for Xklp2 has been shown to be involved in cell division by interaction with microtubule development in cancer cells. Taken together, result of this study suggests that TPX2 may be involved in proliferation and differentiation of human ES cells.