• Molecules and Cells
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• v.45 no.9
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• pp.610-619
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• 2022

Cellular senescence plays a paradoxical role in tumorigenesis through the expression of diverse senescence-associated (SA) secretory phenotypes (SASPs). The heterogeneity of SA gene expression in cancer cells not only promotes cancer stemness but also protects these cells from chemotherapy. Despite the potential correlation between cancer and SA biomarkers, many transcriptional changes across distinct cell populations remain largely unknown. During the past decade, single-cell RNA sequencing (scRNA-seq) technologies have emerged as powerful experimental and analytical tools to dissect such diverse senescence-derived transcriptional changes. Here, we review the recent sequencing efforts that successfully characterized scRNA-seq data obtained from diverse cancer cells and elucidated the role of senescent cells in tumor malignancy. We further highlight the functional implications of SA genes expressed specifically in cancer and stromal cell populations in the tumor microenvironment. Translational research leveraging scRNA-seq profiling of SA genes will facilitate the identification of novel expression patterns underlying cancer susceptibility, providing new therapeutic opportunities in the era of precision medicine.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.481-486
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• 2018

Cosmetics are primarily applied to the skin; therefore, the association of cosmetic dyes with skin diseases or inflammation is a topic of great interest. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that activates dendritic cells to promote Th2 inflammatory immune responses. TSLP is highly expressed in keratinocytes under inflammatory conditions, which suggests that it may play a critical role in the development of skin diseases, such as atopic dermatitis. Therefore, we investigated whether cosmetic dyes influenced the production of TSLP by keratinocytes. Phloxine O, also known as D&C Red No.27, is one of the most common red synthetic pigments and is widely used in colored cosmetics. Our results showed that Phloxine O downregulated phorbol 12-myristate 13-acetate-induced production of TSLP in a murine keratinocyte cell line (PAM212). Phloxine O also suppressed TSLP expression in KCMH-1 cells, which are mouse keratinocytes that constitutively produce high levels of TSLP. To investigate the in vivo effects of Phloxine O, we induced TSLP expression in mouse ear skin by topically applying MC903, a vitamin D3 analogue that is a well-known inducer of atopic dermatitis-like symptoms. Topical application of Phloxine O prevented MC903-induced TSLP production in mouse ear skin, attenuated the acute dermatitis-like symptoms and decreased serum IgE and histamine levels in mice. Suppression of TSLP expression by Phloxine O correlated with reduced expression of OX40 ligand and Th2 cytokines in mouse ear skin. Our results showed that Phloxine O may be beneficial to prevent dermatitis by suppressing the expression of TSLP and Th2 cytokines in skin.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.4
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• pp.289-296
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• 2014

Human adipose-tissue-derived stromal cells (hADSCs) are abundant in adipose tissue and can differentiate into multi-lineage cell types, including adipocytes, osteoblasts, and chondrocytes. In order to define the optimal harvest site of adipose tissue harvest site, we solated hADSCs from different subcutaneous sites (upper abdomen, lower abdomen, and thigh) and compared their proliferation and potential to differentiate into adipocytes and osteoblasts. In addition, this study examined the effect of phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, on proliferation and differentiation of hADSCs to adipocytes or osteoblasts. hADSCs isolated from different subcutaneous depots have a similar growth rate. Fluorescence-activated cell sorting (FACS) analysis showed that the expression levels of CD73 and CD90 were similar between hADSCs from abdomen and thigh regions. However, the expression of CD105 was lower in hADSCs from the thigh than in those from the abdomen. Although the adipogenic differentiation potential of hADSCs from both tissue regions was similar, the osteogenic differentiation potential of hADSCs from the thigh was greater than that of hADSCs from the abdomen. Phorbol 12-myristate 13-acetate (PMA) treatment increased osteogenic differentiation and suppressed adipogenic differentiation of all hADSCs without affecting their growth rate and the treatment of Go6983, a general inhibitor of protein kinase C (PKC) blocked the PMA effect. These findings indicate that the thigh region might be a suitable source of hADSCs for bone regeneration and that the PKC signaling pathway may be involved in the adipogenic and osteogenic differentiation of hADSCs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.3
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• pp.217-220
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• 2010

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is an ulcerative lesion on oral mucosa featuring as a benign mass of self-limiting growth. It can be easily misdiagnosed as squamous cell carcinoma (SCC) due to its long healing period and elevated or rolled-up margin. A 57-year old male patient who visited our department was diagnosed as SCC according to the clinical features, results of positron emission tomography (PET) and magnetic resonance imaging (MRI) of the oral lesion. However, after performing incisional biopsy, histopathologically, there were no atypical cells, but eosinophil and CD 30+ T-cells were clustered in subcutaneous and muscle tissue. It is very significant to consider this reactive lesion in the field of oral and maxillofacial surgery because of its possibility of mistaken as malignant disease. Here, we will report a couple of cases of TUGSE with references and limit of radiographic tools used for diagnosis of head and neck cancer.

• The Journal of Internal Korean Medicine
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• v.39 no.6
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• pp.1181-1190
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• 2018

Objective: This study investigated the effect of purified medical herb extracts such as Alisma canaliculatum and Polyporus umbellatuson adipogenic differentiation of human bone marrow derived mesenchymal stromal stem cells (hBMSCs). Methods: Two different medical herb were extracted using hot distilled water. The optimal concentration of extracts were fixed at 100 ng/ml by means of cell viability and cytotoxic assay. To test the adipogenic differentiation ability of extracts, we induced the adipogenesis of hBMSCs for 21 days. At day 5, the cell was harvested to check mRNA and protein expression level of adipogenic related factors. The efficacy of lipid droplet formation was evaluated using the oil-red O staining method at days 21. Results: Two different medical herb extracts have no toxicity on hBMSCs. And two different medical herb extracts significantly decreased formation of lipid droplet compared with control groups in hBMSCs. The A. canaliculatum extract group showed the lowest mRNA and protein expression level of adipossgenic related transcription factors. This data suggests that extract of A. canaliculatum and P. umbellata decrease the adipogenic differentiation of hBMSCs. Conclusions: Our findings indicate that water-extract of A. canaliculatum and P. umbellata will be useful therapeutic reagents for prevention of obesity related disease such as diabetes, hyperlipidemia, coronary artery disease, and osteoporosis.

• Journal of Animal Science and Technology
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• v.63 no.2
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• pp.426-439
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• 2021

It is already well known that castration improves marbling quality but exact timing of castration is still highly debated in beef cattle production industry. After castration, blood hormonal changes occur in steer and objective of this study was to investigate the effects of growth hormone (GH) levels on adipocyte differentiation in stromal vascular cells (SVCs) and transdifferentiation into adipocytes in C2C12 myoblasts. Total GH concentrations were measured via enzyme-linked immunosorbent assay (ELISA) in 24 male calves and 4 female calves. Cell proliferation, cellular triglyceride (TG) accumulation, and the cell's lipolytic capability were measured in C2C12 myoblasts and SVCs. Myogenic, adipogenic, and brown adipocyte-specific gene expression was measured via real-time polymerase chain reaction (PCR) using SYBR green. Serum GH levels were the highest in late-castrated calves. Treatment with 5 ng/mL GH resulted in greater TG accumulation as well as increased CCAAT-enhancer-binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ expression compared to that after treatment with 15 ng/mL GH. Treatment with 5 ng/mL GH also resulted in lower myogenin (myo)G and myoD expression compared to that after treatment with 15 ng/mL GH. The expression of bone morphogenetic protein (BMP) 7 after treatment with 5 ng/mL GH was higher than that after treatment with 15 ng/mL GH. But carcass characteristics data showed no significant difference between early and late castrated steers. Therefore, our results indicate that castration timing does not seem to be inevitable determinate of carcass qualities, particularly carcass weight and marbling score in Hanwoo beef cattle.

• The Korean Journal of Blood Transfusion
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• v.23 no.2
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• pp.115-126
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• 2012

Background: Umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). We compared the characteristics of MSCs from cryopreserved UC with those from fresh tissues, and demonstrated the possibility of UC cryopreservation for acquisition of MSCs from cryopreserved UC. Methods: Each UC was sliced into two types ($1{\sim}2mm^3$ vs. 0.5 cm), and cryopreserved in liquid nitrogen using different media (autologous cord blood plasma, aCBP vs. RPMI 1640). A fresh aliquot of $1{\sim}2mm^3$-sized UC was used as control tissue. After one week, the cryopreserved tissues were thawed and cultured. For the 0.5 cm UC, a slicing step into $1{\sim}2mm^3$ was needed. Cell count, viability, proliferative activity, and surface antigens were determined from harvested MSCs. Several growth factors (EGF, IGF-1, PDGF, TGF-${\beta}$, bFGF, and VEGF), were measured from the culture supernatant. Results: Eleven UC were enrolled in the study. Efficiencies of obtaining MSCs were higher in cryopreserved UC using RPMI 1640, compared with use of aCBP; the same result was observed for 0.5 cm sized UC, compared with $1{\sim}2mm^3$ sized UC. No difference in proliferative activity was observed between MSCs from fresh and cryopreserved UC. The amount of growth factors in culture supernatant using RPMI 1640 was larger than that of fresh tissues. Conclusion: We obtained growth factors from the supernatant as well as MSCs from cryopreserved UC. As with a cord blood bank, in the future, cryopreservation of UC for acquisition of both MSCs and growth factors would be possible in a time of need.

• 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.

• Archives of Plastic Surgery
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• v.37 no.5
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• pp.509-518
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• 2010

Purpose: Major drawbacks of conventional bone marrow stromal cells (BSCs) transplantation method are mainly caused by direct transplanted cell to host cell interactions. We hypothesized that separation of the transplanted cells by a microporous membrane might inhibit most of the potential adverse effects and induce superior effect. The purpose of the study is to determine the optimal condition of the microporous membrane. Methods: First, BSCs were placed in polyethylene terephthalate (PET) transwell inserts with 3, 8, or $12{\mu}m$ pore size, and cultured in 24 well culture plates. After 5 days, bottoms of the plates were observed for presence of attached BSCs in monolayer and cell numbers were evaluated. Second, BSCs were placed PET, polycarbonate (PCT), and mixed cellulose esters (MCE) transwell inserts with 3 and $8{\mu}m$ pore size, and cultured in 24 well culture plates. After 3 days, the supernatants of the media left in culture plate were analyzed for collagen, vascular endothelial growth factor (VEGF), platelet derived growth factor BB (PDGF-BB), and basic fibroblast growth factor (bFGF). Third, BSCs were placed in 15% and 70% of the PET membrane with $3{\mu}m$ pore size. All the experimental conditions and methods were same as the second study. Results: The optimal pore sizes to prevent BSC leakage were $3{\mu}m$ and $8{\mu}m$. The amounts of type I collagen and three growth factors tested did not show significant differences among PET, PCT, and MCE groups. However, the collagen, VEGF, and bFGF levels were much higher in the high (70%) density group than in the low (15%) density group. Conclusion: This study revealed that the optimal pore size of membrane to prevent direct BSC to recipient cell contact is in between $3{\mu}m$ and $8{\mu}m$. Membrane materials and pore sizes do not influence the collagen and growth factor passage through the membrane. The most striking factor for collagen and growth factor transport is pore density of the membrane.

• Polymer(Korea)
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• v.27 no.5
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• pp.397-404
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• 2003

The interaction of cell adhesive protein and polypeptide with bone marrow stromal stem cells (BMSCs) grown in tissue engineered films and scaffolds were examined. Several proteins or polypeptide known as cell-adhesive were coated adsorption on poly(lactide-co-glycolide) (PLGA) films and scaffolds and adhesion and proliferation behavior of BMSC on those surfaces were compared. The protein and polypeptide used include collagen IV, fibrinogen, laminin, gelatin, fibronectin, and poly(L-lysine). The protein and polypeptide were adsorbed on the PLGA film surfaces with almost monolayer coverage except poly(L-lysine). BMSCs were cultured for 1, 2, and 4 days on the protein- or polypeptide-adsorbed PLGA films and scaffolds. The cell adhesion and proliferation behaviors were assessed by sulforho damine B assay. It was observed that the protein- or polypeptide-adsorbed surfaces showed better cell adhesion and proliferation than the control.