• Molecules and Cells
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• 제38권9호
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• pp.806-813
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• 2015

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

• Reproductive and Developmental Biology
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• 제29권2호
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• pp.93-99
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• 2005

Human embryonic stem cells (hESCs) derived from the inner cell mass of blastocysts have the ability to renew themselves and to differentiate into cell types of all lineage. The present study was carried out to investigate whether the Wnt signaling pathway is related to maintaining self-renewal of hESCs. Glycogen Synthase Kinase 3 (GSK-3) inhibitor, BIO ((2'Z,3'E)-6-Bromoindirubin-3'-oxime) was treated to Miz-hES1 line for activation of Wnt signaling pathway. BIO-nontreated hESCs (control) and BID-treated hESCs were cultured for 5 days in the modified feeder-free system. During the culture of hESCs, differences were observed in the colony morphology between 2 groups. Controls were spread outwards whereas BIO-nontreated hESCs were clumped in the center and the differentiated cells were spreading outwards in the edges. The results of stem cell specific marker staining indicated that control were differentiated in large part whereas BIO-treated hESCs maintain self-renewal in the center of the colony. The results of lineage marker staining suggested that outer cells of the hESC colony were differentiated to the neuronal progenitor cells in both control and BIO-treated hESC. These results indicate that Wnt signaling is related to self-renewal in hESCs. In addition, control group showed higher composition of apoptotic cells $(23.76\%)$ than the BID-treated group $(5.59\%)$. These results indicate that BIO is effective on antapoptosis of hESCs.

• BMB Reports
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• 제51권2호
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• pp.92-97
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• 2018

B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the $NF-{\kappa}B$ family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity. Bcl3 expression is predominantly observed in immature mESCs, but significantly decreased during cell differentiation by LIF depletion and in mESC-derived EBs. Importantly, the knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a significant reduction of proliferation, and the self-renewal of mESCs was demonstrated by alkaline phosphatase staining and clonogenic single cell-derived colony assay. We further examined that Bcl3-mediated regulation of Nanog transcriptional activity in mESCs, which indicated that Bcl3 acts as a transcriptional repressor of Nanog expression in mESCs. In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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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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• 제39권8호
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• pp.619-624
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• 2016

Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all glioblastoma (GBM) cells that are in large part responsible for tumor growth and the high grade of therapeutic resistance that is so characteristic of GBM. MicroRNAs (miR) have been implicated in regulating the expression of oncogenes and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are a potential target for cancer therapy. In the current study, miR-203 expression was reduced in $CD133^+$ GBM-SCs derived from six human GBM biopsies. MicroRNA-203 transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere assay and increased expression of glial and neuronal differentiation markers. In addition, a reduced proliferation rate and an increased rate of apoptosis were observed. Therefore, miR-203 has the potential to reduce features of stemness, specifically in GBM-SCs, and is a logical target for GBM gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8549-8556
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• 2014

Head and neck squamous cell carcinoma (HNSCC) is one of the world top ten most common cancers with its highest occurrence in the Indian subcontinent and different aggressive and etiological behavioural patterns. The scenario is only getting worst with the 5 year survival rates dropping to 50%, persistent treatment failures and frequent cases of relapse/recurrence. One of the major reasons for these failures is the presence of cancer stem cells (CSCs), a small population of cancer cells that are highly tumourigenic, capable of self-renewal and have the ability to differentiate into cells that constitute the bulk of tumours. Notably, recent evidence suggests that cancer stem cells are especially resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. Specific markers for this population have been investigated in HNSCC in the hope of developing a deeper understanding of their role in oral cancer pathogenesis, elucidating novel biomarkers for early diagnosis and newer therapeutic strategies. This review covers the fundamental relevance of almost all the CSC biomarkers established to date with a special emphasis on their impact in the process of oral tumourigenesis and their potential role in improving the diagnosis, prognosis and treatment of OSCC patients.

• Journal of Yeungnam Medical Science
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• 제26권1호
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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.

• Molecules and Cells
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• 제21권3호
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• pp.343-355
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• 2006

Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation, although a wide variety of adult stem cells as well as embryonic stem cells have been identified and stem cell plasticity has recently been reported. To identify genes implicated in the control of the stem cell state as well as the characteristics of each stem cell line, we analyzed the expression profiles of genes in human embryonic, hematopoietic ($CD34^+$ and $CD133^+$), and mesenchymal stem cells using cDNA microarrays, and identified genes that were differentially expressed in specific stem cell populations. In particular we were able to identify potential hESC signature-like genes that encode transcription factors (TFAP2C and MYCN), an RNA binding protein (IMP-3), and a functionally uncharacterized protein (MAGEA4). The overlapping sets of 22 up-regulated and 141 down-regulated genes identified in this study of three human stem cell types may also provide insight into the developmental mechanisms common to all human stem cells. Furthermore, our comprehensive analyses of gene expression profiles in various adult stem cells may help to identify the genetic pathways involved in self-renewal as well as in multi-lineage specific differentiation.

• Journal of Nutrition and Health
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• 제38권10호
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• pp.880-894
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• 2005

The purposes of this study were to a) measure the IC identified of CFMC (contract foodservice management company) ,b) examine IC circumstance of CFMC, c) evaluate practically IC measurement tool of CFMC, and d) present information for selecting an adequate CFMC to clients. The questionnaires of IC measurement were handed out to 108 CFMCs, there composing of main office employees, foodservice managers, customers, and clients of 207 school,38 hospital, and 86 husiness/industry foodservices. The statistical data analysis was completed using SPSS Win (ver 12.0) for descriptive analysis, t-test, Mann-Whitney U test. First, CFMCs had operational experience for an average of 8 years and 8 months, and served an average of 38,540 meals a day. Most of the respondent companies specialized in the school foodservice field and managed an average of 66 clients for the contract period of 2 years and 3 months. Second, the respondent companies had gotten a score of 77.78 points for the total average, 77.7 points in the large enterprise group and 78.1 points in the small and medium-sized enterprise group. Therefore, the minimum number of points for the accrediting license on Qualification is suggested to be over 70 out of a 100 point scale; this study would be serve as reference for the certification license on qualification. On the level of evaluation category, the scores were 14.15 to 20 points on $\ulcorner$finance$\urcorner$, 19.24 to 25 points on $\ulcorner$customer$\urcorner$, 19.33 to 25 points on $\ulcorner$process$\urcorner$, 14.31 to 20 points on $\ulcorner$human resource$\urcorner$, and 8.6 to 10 point on $\ulcorner$renewal and development$\urcorner$ . $\ulcorner$Renewal and development$\urcorner$ and $\ulcorner$customer focus$\urcorner$ received better grades than other evaluation categories. Third, $\ulcorner$Finance$\urcorner$ indicated similar distribution overall. Small and medium-sized companies had lower grades than large companies on 'market ability' of $\ulcorner$customer$\urcorner$ , but, clients of small and medium-sized companies had higher grade for 'client satisfaction' than large companies. Most of the companies supported 'infrastructure support for foodservice operation' of $\ulcorner$process$\urcorner$ by the main office of CFMCs, but, the branch chain offices of CFMCs were not applied efficiently. Large companies made more effort to improve the 'employee ability' of $\ulcorner$human focus$\urcorner$ than small and medium-sized CFMC. The 'research and development cost' of $\ulcorner$renewal and development$\urcorner$ was increased compared to the previous year. In conclusion, if CFMCs were to perform self-evaluation and a routine checkups by utilizing CFMC's IC measuring tool, improvements in CFMC operational capacities as well as foodservice quality can be noted. (Korean J Nutrition 38(10)'880$\sim$894,2005)

• Molecules and Cells
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• 제24권3호
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• pp.343-350
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• 2007

Mesenchymal stem/progenitor cells (MPCs) were isolated from porcine umbilical cord blood (UCB) and their morphology, proliferation, cell cycle status, cell-surface antigen profile and expression of hematopoietic cytokines were characterized. Their capacity to differentiate in vitro into osteocytes, adipocytes and chondrocytes was also evaluated. Primary cultures of adherent porcine MPCs (pMPCs) exhibited a typical fibroblast-like morphology with significant renewal capacity and proliferative ability. Subsequent robust cell growth was indicated by the high percentage of quiescent (G0/G1) cells. The cells expressed the mesenchymal surface markers, CD29, CD49b and CD105, but not the hematopoietic markers, CD45 and CD133 and synthesized hematopoietic cytokines. Over 21 days of induction, the cells differentiated into osteocytes adipocytes and chondrocytes. The expression of lineage specific genes was gradually upregulated during osteogenesis, adipogenesis and chondrogenesis. We conclude that porcine umbilical cord blood contains a population of MPCs capable of self-renewal and of differentiating in vitro into three classical mesenchymal lineages.