• International Journal of Stem Cells
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• v.16 no.3
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• pp.260-268
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• 2023

Intrauterine adhesion (IUA) can occur after trauma to the basal layer of the endometrium, contributing to severe complications in females, such as infertility and amenorrhea. To date, the proposed therapeutic strategies are targeted to relieve IUA, such as hysteroscopic adhesiolysis, Foley catheter balloon, and hyaluronic acid injection have been applied in the clinic. However, these approaches showed limited effects in alleviating endometrial fibrosis and thin endometrium. Mesenchymal stem cells (MSCs) can offer the potential for endometrium regeneration owing to reduce inflammation and release growth factors. On this basis, MSCs have been proposed as promising methods to treat intrauterine adhesion. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles released by stem cells is raising increasing interest. The paracrine effect, mediated by MSCs derived extracellular vehicles (MSC-EVs), has recently been suggested as a mechanism for their therapeutic properties. Here, we summarizes the main pathological mechanisms involved in intrauterine adhesion, the biogenesis and characteristics of extracellular vesicles, explaining how these vesicles could provide new opportunities for MSCs.

• Development and Reproduction
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• v.21 no.1
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• pp.1-10
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• 2017

The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue. To maximize the therapeutic effects of hMSCs, a substantial number of these cells are essential, requiring extensive ex vivo cell expansion. However, hMSCs have a limited lifespan in an in vitro culture condition. The senescence of hMSCs is a double-edged sword from the viewpoint of clinical applications. Although their limited cell proliferation potency protects them from malignant transformation after transplantation, senescence can alter various cell functions including proliferation, differentiation, and migration, that are essential for their therapeutic efficacy. Numerous trials to overcome the limited lifespan of mesenchymal stem cells are discussed.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.197-203
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• 2020

Mesenchymal stem cells in the dental pulp exhibit a tendency for differentiation into various dental lineages and hold great potential as a major conduit for regenerative treatment in dentistry. Although they can be readily isolated from teeth, the exact characteristics of these stem cells have not been fully understood so far. When compared to two-dimensional (2D) cultures, three-dimensional (3D) cultures have the advantage of enriching the stem cell population. Hence, 3D-organoid culture and 3D-sphere culture were applied to dental pulp cells in the current study. Although the establishment of the organoid culture proved unsuccessful, the 3D-sphere culture readily initiated the stable generation of cell aggregates, which continued to grow and could be passaged to the second round. Interestingly, a significant increase in SOX2 expression was detected in the 3D-spheroid culture compared to the 2D culture. These results indicate the enrichment of the stemness-high population in the 3D-sphere culture. Thus, 3D-sphere culture may act as a link between the conventional and 3D-organoid cultures and aid in understanding the characteristics of dental pulp stem cells.

• Journal of Science and Technology Studies
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• v.15 no.1
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• pp.181-214
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• 2015

This study analyzed the characteristics of the politics of technoscience and governance in South Korea, taking advantage of the policy changes on the stem cell research after Hwang's affair. In spite of generally accepted conventional wisdom that stem cell research had been suffering 'crisis' after the Hwang's affair, South Korea succeeded in developing the first and the largest stem cell product in the world. However, considering the fact that the stem cell research capabilities and technological competitiveness of Korea have been assessed as relatively low compared to the development performance, there is a need to extrapolate how such result could be achieved. To answer these questions, we analyzed changes in the R&D expenditure before and after the scandal and verified the 'crisis of stem cell research' following the reduction of financial support from government. From the analysis of literature on the policy reports and news, we described the process of discourse changes in policy and analyzed the characteristics of the politics of technoscience and governance of stem cell research. This study emphasized that the government R&D and regulation policy play the key roles in the development of stem cell research rather than in the technological competitiveness in South Korea. Furthermore, this study argued that democratic governance still does not work under the policy conditions that technocratic decision-making of stem cell research fails to learn from the Hwang's affairs.

• The korean journal of orthodontics
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• v.42 no.5
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• pp.249-254
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• 2012

Objective: To investigate the stem cell-like characteristics of human periodontal ligament (PDL) stromal cells outgrown from orthodontically extracted premolars and to evaluate the potential for myogenic differentiation. Methods: PDL stromal cells were obtained from extracted premolars by using the outgrowth method. Cell morphological features, self-replication capability, and the presence of cell-surface markers, along with osteogenic, adipogenic, and chondrogenic differentiation, were confirmed. In addition, myogenic differentiation was induced by the use of 5-aza-2'-deoxycytidine (5-Aza) for DNA demethylation. Results: PDL stromal cells showed growth patterns and morphological features similar to those of fibroblasts. In contrast, the proliferation rates of premolar PDL stromal cells were similar to those of bone marrow and adipogenic stem cells. PDL stromal cells expressed surface markers of human mesenchymal stem cells (i.e., CD90 and CD105), but not those of hematopoietic stem cells (i.e., CD31 and CD34). PDL stromal cells were differentiated into osteogenic, adipogenic, and chondrogenic lineages. Myotube structures were induced in PDL stromal cells after 5-Aza pretreatment, but not in the absence of 5-Aza pretreatment. Conclusions: PDL stromal cells isolated from extracted premolars can potentially be a good source of postnatal stem cells for oromaxillofacial regeneration in bone and muscle.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.2.1-2.19
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• 2020

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.761-766
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• 2012

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

• 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.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.74-74
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• 2003

Embryonic stem cells have several characteristics suitable for cell replacement therapy. To investigate a possibility of using human embryonic stem cell (hESC) as a carrier of therapeutic gene(s), hESC (MB03) was co-transfected with cDNAS coding for tyrosine hydroxylase (TH) and GTP cyclohydrolase Ⅰ (GTPCH Ⅰ) and bulk-selected using neomycin and hygromycin-B. Successful transfection was confirmed by western immunoblotting and RT-PCR. The genetically modified hESC (bk-THGC) relieved apomorphine-induced asymmetric motor behavior by approximately 54% when grafted into striatum of 6-OHDA-denervated rat brain. The number of rotation, however, increased up to 176+18% in 6 weeks when sham-grafted compared with number of rotation before graft. Immunohistochemical staining revealed that the grafted hESC survived and expressed TH for at least 6 weeks while the experiment was continued.

• Journal of Yeungnam Medical Science
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• v.26 no.1
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• pp.1-14
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• 2009

Human bone marrow-derived mesenchymal stem cells (MSCs) are a rare population of undifferentiated cells that have the capacity of self renewal and the ability to differentiate into mesodermal phenotypes, including osteocytes, chondrocytes, and adipocytes in vitro. Recently, MSCs have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well analyzed. Many reports showed that transplanted MSCs enhanced regeneration as well as functional improvement of damaged organs and tissues. The wide differentiation plasticity of MSCs was expected to contribute to their demonstrated efficacy in a wide variety of experimental animal models and in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for differentiation in tissue repair. This review describes what is known about the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for further applications in regenerative medicine.