• Title/Summary/Keyword: stem-like

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The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling

  • Oh, Jisun;Yoon, Hyo-Jin;Jang, Jeong-Hoon;Kim, Do-Hee;Surh, Young-Joon
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.421-430
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    • 2019
  • Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

A ROCK Inhibitor Blocks the Inhibitory Effect of Chondroitin Sulfate Proteoglycan on Morphological Changes of Mesenchymal Stromal/Stem Cells into Neuron-Like Cells

  • Lim, Hee-Suk;Joe, Young Ae
    • Biomolecules & Therapeutics
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    • v.21 no.6
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    • pp.447-453
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    • 2013
  • Chondroitin sulfate proteoglycan (CSPG) inhibits neurite outgrowth of various neuronal cell types, and CSPG-associated inhibition of neurite outgrowth is mediated by the Rho/ROCK pathway. Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and have been shown to differentiate into neuron-like cells by co-treatment with the ROCK inhibitor Y27632 and the hypoxia condition mimicking agent $CoCl_2$. In this study, we addressed the hypothesis that a ROCK inhibitor might be beneficial to regenerate neurons during stem cell therapy by preventing transplanted MSCs from inhibition by CSPG in damaged tissues. Indeed, dose-dependent inhibition by CSPG pretreatment was observed during morphological changes of Wharton's jelly-derived MSCs (WJ-MSCs) induced by Y27632 alone. The formation of neurite-like structures was significantly inhibited when WJ-MSCs were pre-treated with CSPG before induction under Y27632 plus $CoCl_2$ conditions, and pretreatment with a protein kinase C inhibitor reversed such inhibition. However, CSPG treatment resulted in no significant inhibition of the WJ-MSC morphological changes into neuron-like cells after initiating induction by Y27632 plus $CoCl_2$. No marked changes were detected in expression levels of neuronal markers induced by Y27632 plus $CoCl_2$ upon CSPG treatment. CSPG also blocked the morphological changes of human bone marrow-derived MSCs into neuron-like cells under other neuronal induction condition without the ROCK inhibitor, and Y27632 pre-treatment blocked the inhibitory effect of CSPG. These results suggest that a ROCK inhibitor can be efficiently used in stem cell therapy for neuronal induction by avoiding hindrance from CSPG.

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.

External and Internal Morphological Standard of Original Plants and Herbal States in Pogostemonis and Agastachis Herba (廣藿香과 土藿香의 外部 및 內部形態硏究)

  • Kang, Jun-hyug;Choi, Jeong;Ju, Young-sung
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.16 no.3
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    • pp.164-184
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    • 2003
  • Objectives : This study was designed to establish a characteristic discrimination of internal and external morphological standard of original plants and herbal states in Pogostemonis and Agastachis Herba. Methods : In this studies, the external-internal morphological standards were determined by using stereoscope and butanol series. Results : 1. The external characteristics: Pogostemon cablin has hairs and brown-like in stem, elliptical fruit. On the other hand, Agastache rugosa has no hairs and red-like in stem, obovatic trigone fruit. 2. The physical characteristics: Pogostemon cablin is gray in whole, has hairs in stem and numerous hairs of ash in leaf. On the other hand, Agastache rugosa is yellow-green in whole, has no hairs in stem. Specially the latter has deep-green colour and numerous hairs presenting mostly at lower epidermis in leaf. 3. The physical characteristics in currents: Pogostemon cablin is brown, has hairs and round-like stem. On the other hand, Agastache rugosa is green or yellow-green, has no hairs and tetragon in stem. 4. The internal characteristics: Pogostemon cablin has progressed spongy tissue in epidermal cell of leaf and many rank of epidermal cell in stem. On other hand, Agastache rugosa has I rank palisade tissue in leaf and few rank of epidermal cell in stem. In the external shape, it was possible that herbs were distinguished according to artificial cIassification and that same genus-degree of relatedness among herbs could be distinguished by more precise and active observation. In the shape of real herbs, I compared current herbs in market with original herbs which were just collected or were on the course of drying. In addition, it was possible that the internal shape could be identified by using microscope after butanol series. Conclusion : Though it was impossible to make distinction of herbs which are not current in my search contents, this search contents will be a standard for applying herbs in the future. An Additional standard establishment including physiochemical reaction and gene research is required in order to supplement the fault of this search.

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Establishment of Stem-like Cells from Human Umbilical Cord Vein

  • Park, Seah;Kim, Kyung-Suk;Kim, Haekwon;Do, Byung-Rok;Kwon, Hyuck-Chan;Kim, Hyun-Ok;Im, Jung-Ae
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.78-78
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    • 2003
  • Adult stem cells can make identical copies of themselves for long periods of time. They also give rise to many differentiated mature cell types that have characteristic morphology and specialized function. Human adult stem cells are the attractive raw materials for the cell/tissue therapy, however, it is not easy to get from the adult tissues. In the present study, we tried to isolate a cell population derived from human umbilical cord vein which has been discarded after birth. The cells were isolated after treatment of the umbilical vein with collagenase or trypsin. After 3 days of culture, two kinds of cell populations were found consisting of adherent cells with endothelial cell-like and fibroblast-like morphology, respectively. When these cells were subcultured 12 times over a period of 3 months, almost cells appeared uniformly to exhibit fibroblastoid morphology which was different from that of mesenchymal stem cells obtained from human bone marrow The results of RT-PCR analyses showed distinct expression of BMP-4, oct-4, and SCF genes but not of GATA, PAX-6 and Brachyury genes. On immunohistochemical staining, the cells were negative for the von Willebrand factor(vWF), alpha-smooth muscle actin and placental alkaline phosphatase. From these observations, it is suggested that stem-like cells might be present in human umbilical cord vein.

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Kaposi's Sarcoma-Associated Herpesvirus Infection Modulates the Proliferation of Glioma Stem-Like Cells

  • Jeon, Hyungtaek;Kang, Yun Hee;Yoo, Seung-Min;Park, Myung-Jin;Park, Jong Bae;Lee, Seung-Hoon;Lee, Myung-Shin
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.165-174
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    • 2018
  • Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma. However, a direct link between KSHV infection and glioblastoma is currently not known. In this study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV to establish an in vitro cell model for KSHV-infected glioblastoma cells and glioma stem-like cells in order to identify virologic outcomes that overlap with markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs were successfully established. Additionally, using these cell models, we found that KSHV infection modulates the proliferation of glioma stem-like cells.

Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells

  • Ding, Bo;Liu, Ping;Liu, Wen;Sun, Ping;Wang, Chun-Ling
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3629-3633
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    • 2015
  • Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Kr$\ddot{u}$ppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of K LF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.

Non Linear Finite Element Analyses of Ceramic/Ceramic Pairs of Total Hip Replacements Using High Trauma-Like Loads (고응력 외상에의한 고관절용 세라믹/세라믹 쌍의 비선형 유한요소법 분석)

  • Karyo, Daniel;Lee, Su-Wan
    • Proceedings of the Korean Institute of Surface Engineering Conference
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    • 2005.11a
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    • pp.179-180
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    • 2005
  • Non linear finite element analyses were performed in various configurations of stem-ball head. High stresses were found for the cases when the stem tended to penetrate less into the ball head. An upgraded design of the cone may improve the loading of the ball head to resist trauma-like loading more effectively than manipulating the ball diameter. When the surgeon needs to use small ball heads (i.e. 22 mm), the use of zirconia seems to be appropriate also. After simulating a trauma like loading of the materials, it was found that the deepness of the cone to locate the stem is of major importance for the performance of the device. Further work, considering more sizes for the cone design should be performed in order to determine an optimal depth for the cone in relation to the diameter of the ball head. Also the simulation of contacts pairs including polyethylene and CoCr is important for further research.

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Embryo-derived stem cells -a system is emerging

  • Binas, B.
    • BMB Reports
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    • v.42 no.2
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    • pp.72-80
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    • 2009
  • In mammals, major progress has recently been made with the dissection of early embryonic cell specification, the isolation of stem cells from early embryos, and the production of embryonic-like stem cells from adult cells. These studies have overcome long-standing species barriers for stem cell isolation, have revealed a deeper than expected similarity of embryo cell types across species, and have led to a better understanding of the lineage identities of embryo-derived stem cells, most notably of mouse and human embryonic stem (ES) cells. Thus, it has now become possible to propose a species-overarching classification of embryo stem cells, which are defined here as pre- to early post-implantation conceptus-derived stem cell types that maintain embryonic lineage identities in vitro. The present article gives an overview of these cells and discusses their relationships with each other and the conceptus. Consequently, it is debated whether further embryo stem cell types await isolation, and the study of the earliest extraembryonically committed stem cells is identified as a promising new research field.