• Journal of Life Science
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• v.34 no.3
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• pp.170-178
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• 2024

Adipose-derived stem cells (ADSCs) are capable of differentiation into multiple lineages of cells, which has attracted attention for clinical therapy. However, ADSCs have poor proliferation capacity and a short life span in culture, which is an impediment in the application to clinical use. Previously, to overcome growth disadvantages, we had established an immortalized ADSC line (ADSC-T) by introducing the SV40 T antigen coding gene into primary human ADSC. In the present study, we evaluated the differentiation potential of this cell line and assessed the anti-inflammatory effect of its conditioned medium (CM). ADSC-T appeared to maintain the differentiation potential into adipocyte and chondrocyte. The CM of ADSC-T suppressed the NF-κB activity and its target gene expression of COX-2 and iNOS. Furthermore, the phosphorylations of MAPKs, including ERK, JNK and p38, were suppressed by the ADSC-T CM. The expressions of pro-inflammatory cytokines such as TGF-β, TNF-α, IL-6, and IL-13 were also suppressed by the CM of ADSC-T. In the Nc/Nga atopic model mice, the CM showed therapeutic effect on DNCB-induced atopic dermatitis. These results indicate that the immortalized ADSC-T maintains the beneficial properties of primary ADSC and could be a versatile cell source for not only research into ADSC but also for production of CM suitable for clinical application.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.166-174
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• 2002

Background: Human umbilical cord bloods, which could be taken during the delivery are utilized as a source of hematopoietic stem cells. Also in cord blood, there are several kinds of stem cells such as endothelial and mesenchymal stem cells. Methods: We isolated the mesenchymal stem cells from human umbilical cord bloods and confirmed the differentiation of these cells into osteoblast progenitor cells. The mesenchymal stem cells derived from umbilical cord blood have the ability to differentiate into specific tissue cells, which is one of characteristics of stem cells. These cells were originated from the multipolar shaped cells out of adherent cells of the umbilical cord blood mononuclear cell culture. Results: The mesenchymal stem cells expressed cell surface antigen CD13, CD90, CD102, CD105, ${\alpha}$-smooth muscle actin and cytoplasmic antigen vimentine. Having cultrued these cells in bone formation media, we observed the formation of extracellular matrix and the expression of alkaline phosphatase and of mRNA of cbfa-1, ostoecalcin and type I collagen. Conclusion: From these results we concluded that the cells isolated from the umbilical cord blood were mesenchymal stem cells, which we could differentiate into osteoblast when cultured in bone formation media. In short, it is suggested that these cells could be used as a new source of stem cells, which has the probability to alternate the embryonic stem cells.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.307.2-308
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• 2002

Acharan sulfate. a new glycosaminoglycan(GAG) isolated from the giant African snail Achatina fulica. was shown to have antitumor activity in vivo. To elucidate the mechanisms for the antitumor activity. we examined its impact on professional antigen presenting cells such as macrophages and dendritic cells (DCs). Acharan sulfate stimulated cytokine production (TNF-a and IL -1b). nitric oxide release. and morphological changes in a dose dependent manner on a macrophage cell Line Raw 264.7 cells. The differentiation-inducing activity of acharan sulfate was examined on immature DCs. Immature DCs were generated from mouse bone marrow (BM) cells by culturing with GM-CSF and IL-4, and then stimulated with acharan sulfate. The resultant DCs were then examined for funcional and phenotypic properties. It was found that acharan sulfate could induce functional maturation of immature DCs as determined by increased allogenic mixed lymphocyte reaction (MLR) and IL-12 production. Phenotypic. analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2 and CD40 also confirmed that acharan sulfate could induce maturation of immature DCs. These results suggest that that the antitumor activity of acharan sulfate is at least in part due to activation adn induction of differentiation of professinal antigen presenting cells. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3627-3630
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• 2012

The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously. Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN). Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing doses of 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processed for histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twenty hepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferating cell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected in hepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observed in normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells, showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with co-localization. Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors and many tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-induced tumors, possibly associated with cell proliferation.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.111-120
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• 2015

Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.2.1-2.19
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• 2023

Immune diversification helps protect the host against a myriad of pathogens. CD8⁺ T cells are essential adaptive immune cells that inhibit the spread of pathogens by inducing apoptosis in infected host cells, ultimately ensuring complete elimination of infectious pathogens and suppressing disease development. Accordingly, numerous studies have been conducted to elucidate the mechanisms underlying CD8⁺ T cell activation, proliferation, and differentiation into effector and memory cells, and to identify various intrinsic and extrinsic factors regulating these processes. The current knowledge accumulated through these studies has led to a huge breakthrough in understanding the existence of heterogeneity in CD8⁺ T cell populations during immune response and the principles underlying this heterogeneity. As the heterogeneity in effector/memory phases has been extensively reviewed elsewhere, in the current review, we focus on CD8⁺ T cells in a "naive" state, introducing recent studies dealing with the heterogeneity of naive CD8⁺ T cells and discussing the factors that contribute to such heterogeneity. We also discuss how this heterogeneity contributes to establishing the immense complexity of antigen-specific CD8⁺ T cell response.

• IMMUNE NETWORK
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• v.16 no.5
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• pp.281-285
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• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.53-60
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• 2001

Background: The human mic2 gene is a pseudoautosomal gene that encodes a cell surface antigen, CD99. High levels of CD99 constitute a tumor marker in Ewing s sarcoma (ES). We have recently demonstrated that CD99-induced apoptosis occurs only in undifferentiated ES cells, not in differentiated ES cells, raising the possibility of the involvement of CD99 in neural ontogeny. Methods: To elucidate the relations between the expression of CD99 and the differentiation of neural cells and the mechanism by which the expression of CD99 is regulated, we analyzed the differential patterns of CD99 expression in SH-SY5Y by treatment of 12-O-tetradecanoyl-13-phorbol acetate (TPA) and retinoic acid. In addition, to explore the transcriptional activity of CD 99 during neural cell differentiation, SH-SY5Y cells were transiently transfected with a CD99 promoter-driven luciferase construct, and treated with the inducers. Results: In immunoblotting and flow cytometry, the expression level of CD99 was increased on differentiated SH-SY5Y cells induced by TPA and retinoic acid. The luciferase activity was elevated by the treatment with TPA, known to mature SH-SY5Y cells toward a sympathetic neuronal lineage, whereas retinoic acid inducing a sympathetic chromaffin lineage displayed little effect. Conclusion: The result indicates that CD99 might be expressed only on cells maturing toward a neuronal lineage among differentiating primitive neuronal cells. In addition, the expression of CD99 seems to be regulated at the transcriptional level during the differentiation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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• pp.327-333
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• 2006

Future cell-based therapies such as tissue engineering will benefit from a source of autogenous pluripotent stem cells. There are embryonic stem cells (ESC) and autologous adult stem cells, two general types of stem cells potentilally useful for these applications. But practical use of ESC is limited due to potential problems of cell regulation and ethical considerations. To get bone marrow stem cells is relatively burden to patients because of pain, anesthesia requirement. The ideal stem cells are required of such as the following advantages: easy to obtain, minimal patient discomfort and a capability of yielding enough cell numbers. Adipose autologus tissue taken from intraoral fatty pad or abdomen may represent such a source. Our study designed to demonstrate the ability of human adipose tissue-derived stromal cells (hATSC) from human abdominal adipose tissue diffentiating into osteocyte and adipocyte under culture in vitro conditions. As a result of experiment, we identified stromal cell derived adipose tissue has the multilineage potentiality under appropriate culture conditions. And the adipose stromal cells expressed several mesenchymal stem cell related antigen (CD29, CD44) reactions. Secondary, we compared the culture results of a group of hATSC stimulated with TGF-${\beta}$1, bFGF with a hATSC group without growth factors to confirm whether cytokines have a important role of the proliferation in osteogenic differentiation. The role of cytokines such as TGF-${\beta}$1, bFGF increased hATSC's osteogenic differentiation especially when TGF-${\beta}$1 and bFGF were used together. These results suggest that adipose stromal cells with growth factors could be efficiently available for cell-based bone regeneration.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.189-194
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• 2011

Nardostachys chinensis (N. Chinensis) belonging to the family Valerianaceae have been used in traditional medicine to elicit stomachic and sedative effects. The present study investigated the effects of water extract of N. Chinensis in human lymphoma U937 cells. The proliferation of U937 cells was decreased by N. Chinensis. Anti-proliferative effect of N. Chinensis on U937 cells was associated with G0/G1 phase arrest, which was mediated by regulating the expression of p21 and p27 protein. In addition, the levels of CDK2, CDK4, CDK6, Cyclin D3, and Cyclin A were decreased, but Cyclin D1, Cyclin D2 and Cyclin E were essentially undetectable. N. Chinensis induced the differentiation of U937 as shown by increased expression of differentiation surface antigen CD11b, but not CD14. Taken together, these results demonstrated that N. Chinensis potently inhibits the proliferation of U937 cells via the G0/G1 phase cell cycle arrest in association with p21 and p27, and induces granulocytic differentiation.