• Molecules and Cells
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• v.40 no.1
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• pp.54-65
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• 2017

Although cancer/testis antigen DDX53 confers anti-cancer drug-resistance, the effect of DDX53 on cancer stem cell-like properties and autophagy remains unknown. MDA-MB-231 ($CD133^+$) cells showed higher expression of DDX53, SOX-2, NANOG and MDR1 than MDA-MB-231 ($CD133^-$). DDX53 increased in vitro self-renewal activity of MCF-7 while decreasing expression of DDX53 by siRNA lowered in vitro self-renewal activity of MDA-MB-231. DDX53 showed an interaction with EGFR and binding to the promoter sequences of EGFR. DDX53 induced resistance to anti-cancer drugs in MCF-7 cells while decreased expression of DDX53 by siRNA increased the sensitivity of MDA-MB-231 to anti-cancer drugs. Negative regulators of DDX53, such as miR-200b and miR-217, increased the sensitivity of MDA-MB-231 to anti-cancer drugs. MDA-MB-231 showed higher expression of autophagy marker proteins such as ATG-5, $pBeclin1^{Ser15}$ and LC-3I/II compared with MCF-7. DDX53 regulated the expression of marker proteins of autophagy in MCF-7 and MDA-MB-231 cells. miR-200b and miR-217 negatively regulated the expression of autophagy marker proteins. Chromatin immunoprecipitation assays showed the direct regulation of ATG-5. The decreased expression of ATG-5 by siRNA increased the sensitivity to anti-cancer drugs in MDA-MB-231 cells. In conclusion, DDX53 promotes stem cell-like properties, autophagy, and confers resistance to anti-cancer drugs in breast cancer cells.

• Clinical and Experimental Otorhinolaryngology
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• v.11 no.4
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• pp.224-232
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• 2018

Objectives. Spiral ganglion neurons (SGNs) include potential endogenous progenitor populations for the regeneration of the peripheral auditory system. However, whether these populations are present in adult mice is largely unknown. We examined the presence and characteristics of SGN-neural stem cells (NSCs) in mice as a function of age. Methods. The expression of Nestin and Ki67 was examined in sequentially dissected cochlear modiolar tissues from mice of different ages (from postnatal day to 24 weeks) and the sphere-forming populations from the SGNs were isolated and differentiated into different cell types. Results. There were significant decreases in Nestin and Ki67 double-positive mitotic progenitor cells in vivo with increasing mouse age. The SGNs formed spheres exhibiting self-renewing activity and multipotent capacity, which were seen in NSCs and were capable of differentiating into neuron and glial cell types. The SGN spheres derived from mice at an early age (postnatal day or 2 weeks) contained more mitotic stem cells than those from mice at a late age. Conclusion. Our findings showed the presence of self-renewing and proliferative subtypes of SGN-NSCs which might serve as a promising source for the regeneration of auditory neurons even in adult mice.

• Korean Journal of Veterinary Research
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• v.53 no.2
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• pp.109-115
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• 2013

Cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumorinitiating cells. These cells possess the ability to self-renew and proliferate, and are thus able to form the tumor. In the present study cells that correspond to cancer stem cells in mammary and liver cancers in animals were identified by the expression of CD133, CD44, CK7, and OCT4 using immunochemistry. As a result, we found with CD133+ and CD44+ cancer stem cell-like phenotypes in mouse and canine hepatocellular carcinoma and canine mammary gland tumors. However, CK7+ and OCT4+ cells were not identified in animal mammary and liver cancer. CD133+ and CD44+ cells are wellknown stem cell lines and play key roles in development and metastasis in human cancer. These findings suggest that cancer stem cells are involved in animal tumorigenesis and may provide insight into mechanisms in cancer development as well as cancer diagnostics.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.2
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• pp.54-61
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• 2023

Background: Germ cells undergo towards male or female pathways to produce spermatozoa or oocyte respectively which is essential for sexual reproduction. Mesenchymal stem cells (MSCs) have the potential of trans-differentiation to the multiple cell lineages. Methods: Herein, rat MSCs were isolated from bone marrow and characterized by their morphological features, expression of MSC surface markers, and in vitro differentiation capability. Results: Thereafter, we induced these cells only by retinoic acid supplementation in MSC medium and, could able to show that bone marrow derived MSCs are capable to trans-differentiate into male germ cell-like cells in vitro. We characterized these cells by morphological changes, the expressions of germ cell specific markers by immunophenotyping and molecular biology tools. Further, we quantified these differentiated cells. Conclusions: This study suggests that only Retinoic acid in culture medium could induce bone marrow MSCs to differentiate germ cell-like cells in vitro. This basic method of germ cell generation might be helpful in the prospective applications of this technology.

• Bulletin of the Korean Chemical Society
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• v.33 no.6
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• pp.1983-1988
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• 2012

Stem cell transplantation is emerging as a possible new treatment for liver cirrhosis, and recent animal studies have documented the benefits of stem cell therapy in a hepatic fibrosis model. However, the underlying mechanism of stem cell therapy is still unclear. Among the proposed mechanisms, the cell replacement mechanism is the oldest and most important, in which permanently damaged tissue can be replaced by normal tissue to restore function. In the present study, Cy5.5-labeled superparamagnetic iron oxide (SPIO) was used to label human mesenchymal stem cells. The uptake of fluorescently labeled nanoparticles enabled the detection and monitoring of the transplanted stem cells; therefore, we confirmed the direct incorporation and differentiation of SPIO into the hepatocyte-like transplanted stem cells by detecting human tyrosine aminotransferase (TAT), well-known enzymatic marker for hepatocyte-specific differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5947-5954
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• 2012

The cancer stem cell (CSC) model states that cancers are organized in cellular hierarchies, which explains the functional heterogeneity often seen in tumors. Like normal tissue stem cells, CSCs are capable of self-renewal, either by symmetric or asymmetric cell division, and have the exclusive ability to reproduce malignant tumors indefinitely. Current systemic cancer therapies frequently fail to eliminate advanced tumors, which may be due to their inability to effectively target CSC populations. It has been shown that embryonic pathways such as Wnt, Hedgehog, and Notch control self-renewal and cell fate decisions of stem cells and progenitor cells. These are evolutionary conserved pathways, involved in CSC maintenance. Targeting these pathways may be effective in eradicating CSCs and preventing chemotherapy or radiotherapy resistance.

• 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.

• Molecules and Cells
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• v.39 no.11
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• pp.790-796
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• 2016

Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed mesenchymal stem cell (MSC)-like characteristics including the expression of surface antigens and in vitro osteogenic and adipogenic differentiation potentials. Moreover, SHEDs were positive for NG2, ${\alpha}$-smooth muscle actin (SMA), platelet-derived growth factor receptor beta ($PDGFR{\beta}$), and CD146 as pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs were transplanted into immunodeficient mouse using Matrigel with or without human umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or HUVECs alone resulted in no formation of vessel-like structures with enough red blood cells. However, when SHEDs and HUVECs were transplanted together, extensive vessel-like structures were formed. The presence of murine erythrocytes within lumens suggested the formation of anastomoses between newly formed vessel-like structures in Matrigel plug and the host circulatory system. To understand underlying mechanisms of in vivo angiogenesis, the expression of angiogenic cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and HUVECs. SHEDs showed higher expression of1VEGF, SDF-$1{\alpha}$, and $PDGFR{\beta}$ than HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors, CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested reciprocal interactions between SHEDs and HUVECs and their involvement during in vivo angiogenesis. In conclusion, SHEDs could be a feasible source of perivascular cells for in vivo angiogenesis.

• BMB Reports
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• v.53 no.12
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• pp.622-627
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• 2020

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

• Journal of Korean Neurosurgical Society
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• v.30 no.8
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• pp.963-969
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• 2001

Objectives : Cord blood stem cells have been widely used as donor cells for bone marrow transplantation recently. These cells can give rise to a variety of hematopoietic lineages to repopulate the blood. Recent observations reveal that some bone marrow cells and bone marrow stromal cells(MSCs) can grow to become either neurons or glial cells. It is, however, unclear whether or not there exists stems cells which can differentiate into neurons in the blood during the early stages of postnatal life. Methods : Human cord blood stem cells were prepared from human placenta after full term delivery. To induce neuronal differentiation of stem cells, ${\beta}$-mercaptoethanol was treated. To confirm the neuro-glial characteristics of differentiated stem cells, immunocytochemical stain for NeuN, neurofilament, glial fibrillary acidic protein(GFAP), microtubule associated protein2(MAP2) was performed. RT-PCR was performed for detecting nestin mRNA and MAP2 mRNA. Results : We showed in this experiment that neuro-glial markers(NeuN, neurofilament, MAP2, GFAP) were expressed and axon-like cytoplasmic processes are elaborated in the cultured human cord blood stem cells prepared from new born placenta after full term delivery. Nestin mRNA was also detected in fresh cord blood monocytes. Conclusions : These results suggest that human cord blood derived stem cells may be potential sources of neurons in early postnatal life.