• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.196-203
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• 2013

Recent accumulating studies have reported that hypoxic preconditioning during ex vivo expansion enhanced the self-renewal or differentiation of various stem cells and provide an important strategy for the adequate modulation of oxygen in culture conditions, which might increase the functional bioactivity of these cells for cardiac regeneration. In this study, we proposed a novel priming protocol to increase the functional bioactivity of cardiac progenitor cells (CPCs) for the treatment of cardiac regeneration. Firstly, patient-derived c-$kit^+$ CPCs isolated from the atrium of human hearts by enzymatic digestion and secondly, pivotal target molecules identified their differentiation into specific cell lineages. We observed that hCPCs, in response to hypoxia, strongly activated ERK phosphorylation in ex vivo culture conditioning. Interestingly, pre-treatment with an ERK inhibitor, U0126, significantly enhanced cellular proliferation and tubular formation capacities of CPCs. Furthermore, we observed that hCPCs efficiently maintained the expression of the c-kit, a typical stem cell marker of CPCs, under both hypoxic conditioning and ERK inhibition. We also show that hCPCs, after preconditioning of both hypoxic and ERK inhibition, are capable of differentiating into smooth muscle cells (SMCs) and cardiomyocytes (CMs), but not endothelial cells (ECs), as demonstrated by the strong expression of ${\alpha}$-SMA, Nkx2.5, and cTnT, respectively. From our results, we conclude that the functional bioactivity of patient-derived hCPCs and their ability to differentiate into SMCs and CMs can be efficiently increased under specifically defined culture conditions such as short-term hypoxic preconditioning and ERK inhibition.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.2
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• pp.97-108
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• 2011

Cancer stem cells have stem cell-like features, such as the ability for self-renewal and differentiation but show unlimited growth because they have the lost normal regulation of cell growth. Cancer stem cells and normal stem cells have similar features. They show high motility, diversity of progeny, robust proliferative potential, association with blood vessels, immature expression profiles, nestin expression, epidermal growth factor (EGF)-receptor expression, phosphatase and tensin homolog (PTEN) expression, hedgehog pathway activity, telomerase activity, and Wnt pathway activity. On the other hand, with cancer cells, some of these signaling pathways are abnormally modified. In 1875, Cohnheim suggested the concept of cancer stem cells. Recently, evidence for the existence of cancer stem cells was identified. In 1994, the cancer stem cells' specific cell surface marker for leukemia was identified. Since then, other specific cell surface markers for cancer stem cells in solid tumors (e.g. breast and colon cancer) have been identified. In oral cancer, studies on cancer stem cells have been performed mainly with squamous cell carcinomas. Oral cancer specific cell surface markers, which are genes strongly expressed in oral cancer and cancer stem cell specific side populations, have been identified. Cancer stem cells are resistant to radiotherapy and chemotherapy. Therefore, to eliminate malignant tumors efficiently and reduce the recurrence rate, therapy targeting cancer stem cells needs to be performed. Currently, studies targeting the cancer stem cells' specific signaling pathways, telomerase and tumor vasculatures are being done.

• BMB Reports
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• v.54 no.10
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• pp.505-515
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• 2021

Human pluripotent stem cells (hPSCs) include human embryonic stem cells (hESCs) derived from blastocysts and human induced pluripotent stem cells (hiPSCs) generated from somatic cell reprogramming. Due to their self-renewal ability and pluripotent differentiation potential, hPSCs serve as an excellent experimental platform for human development, disease modeling, drug screening, and cell therapy. Traditionally, hPSCs were considered to form a homogenous population. However, recent advances in single cell technologies revealed a high degree of variability between individual cells within a hPSC population. Different types of heterogeneity can arise by genetic and epigenetic abnormalities associated with long-term in vitro culture and somatic cell reprogramming. These variations initially appear in a rare population of cells. However, some cancer-related variations can confer growth advantages to the affected cells and alter cellular phenotypes, which raises significant concerns in hPSC applications. In contrast, other types of heterogeneity are related to intrinsic features of hPSCs such as asynchronous cell cycle and spatial asymmetry in cell adhesion. A growing body of evidence suggests that hPSCs exploit the intrinsic heterogeneity to produce multiple lineages during differentiation. This idea offers a new concept of pluripotency with single cell heterogeneity as an integral element. Collectively, single cell heterogeneity is Janus-faced in hPSC function and application. Harmful heterogeneity has to be minimized by improving culture conditions and screening methods. However, other heterogeneity that is integral for pluripotency can be utilized to control hPSC proliferation and differentiation.

• Korean Journal of Veterinary Research
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• v.58 no.4
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• pp.201-209
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• 2018

Canine mammary tumors are among the most frequently observed cutaneous tumors in female dogs. Cancer stem cells (CSCs), referred to as tumor-initiating cells, are thought to have properties similar to normal stem cells such as the ability to self-renewal and to differentiate into various cell types. Biological understanding of CSCs and the critical pathways involved in their maintenance are important in research and therapy for mammary tumors. We conducted the present study on sphere formation from REM134 cells by using methylcellulose to produce tumorspheres on a large scale and compared the specific markers of the spheres-formed and plating-cultured REM134 cells. The results revealed that the tumorspheres cultured in methylcellulose had higher seeding density and improved morphology compared to those produced in normal sphere formation medium. Expression levels of stemness markers and CSC-related markers were higher in tumorsphere-forming cells than in plating-cultured cells. Subsequently, we transplanted the tumorsphere-forming and plating-cultured cells into female nude mice to examine their tumorigenic potential. Tumor volume increased rapidly in mice transplanted with tumorsphere-derived cells compared to plating-cultured cells. We observed a novel sphere-forming condition for REM134 cells and showed that REM134 cell tumorspheres can exhibit improved CSC properties.

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.1
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• pp.2-9
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• 2019

Because mesenchymal stem cells (MSCs) maintain distinct capacities with respect to self-renewal, differentiation ability and immunomodulatory function, they have been highly considered as the therapeutic agents for cell-based clinical application. Of particular, differentiation condition alters characteristics of MSCs, including cellular morphology, expression of gene/protein and cell surface molecule, immunological property and apoptosis. However, the previous results for differentiation-related apoptosis in MSCs have still remained controversial due to varied outcomes. Therefore, the present study aimed to disclose periodical alterations of pro- and anti-apoptosis in MSCs under differentiation inductions. The human dental pulp-derived MSCs (DP-MSCs) were differentiated into adipocytes and osteoblasts during early (1 week), middle (2 weeks) and late (3 weeks) stages, and were investigated on their apoptosis-related changes by Annexin V assay, qRT-PCR and western blotting. The ratio of apoptotic cell population was significantly (p < 0.05) elevated during the early to middle stages of differentiations but recovered up to the similar level of undifferentiated state at the late stage of differentiation. In the expression of mRNA and protein, whereas expressions of pro-apoptosis-related makers (BAX and BAK) were not altered in any kind and duration of differentiation inductions, anti-apoptosis marker (BCL2) was significantly (p < 0.05) elevated even at the early stage of differentiations. The recovery of apoptotic cell population at the late stage of differentiation is expected to be associated with the response by elevation of anti-apoptotic molecules. The present study may contribute on understanding for cellular mechanism in differentiation of MSCs and provide background data in clinical application of MSCs in the animal biotechnology to develop effective and safe therapeutic strategy.

• Journal of Life Science
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• v.32 no.6
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• pp.468-475
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• 2022

The functional distinction between stem and progenitor cells is well established in several tissues, particularly in the blood. There, hematopoietic stem cells preserve their self-renewal potential and reconstitution ability in the bone marrow niche. Bone marrow represents a unique setting in which to examine how stroma influences tissue function. It was the setting in which the experimental definition of a niche was first provided in mammalian stem cell biology and where clear evidence for non-cell-autonomous oncogenesis was first defined. The relationship between bone and blood is ancient as all animals since the divergence of fish that have bones and blood, make blood in their bones. This long coevolution engendered complex interrelationships, including the first proposed and first experimentally defined niche for stem cells in mammals. Multiple bone marrow stromal cell types serve as regulators of hematopoiesis, and the dysfunction of some causes myelodysplasia and leukemia. However, no comprehensive atlas of stromal subpopulations exists. Therefore, we think these data point to something of importance, such as how the needs and challenges of the organism become translated down to distinct cell types that critically govern specific functions within tissues and do so at the level of a single molecule. We think this will be of broad interest to those focusing on systems biology and the physiology of organisms, particularly those seeking a molecular basis for understanding cell and tissue behavior. We summarized the current and emerging concepts of hematopoietic stem cells and bone marrow niche.

• Journal of Plant Biotechnology
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• v.33 no.3
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• pp.195-207
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• 2006

Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

• Journal of Korean Home Economics Education Association
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• v.24 no.2
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• pp.117-134
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• 2012

The purpose of this study was to identify the stage of concern, the level of use, and the innovation configuration of Home Economics teachers regarding creativity and personality education in Home Economics(HE) classes. The survey questionnaires were sent through mails and e-mails to middle-school HE teachers in the whole country selected by systematic sampling and convenience sampling. Questionnaires of the stages of concern and the levels of use developed by Hall(1987) were used in this study. 187 data were used for the final analysis by using SPSS/window(12.0) program. The results of the study were as following: First, for the stage of concerns of HE teachers on creativity and personality education, the information stage of concerns(85.51) was the one with the highest response rate and the next high in the following order: the management stage of concerns(81.88), the awareness stage of concerns(82.15), the refocusing stage of concerns(68.80), the collaboration stage of concerns(61.97), and the consequence stage of concerns(59.76). Second, the levels of use of HE teachers on creativity and personality education was highest with the mechanical levels(level 3; 21.4%) and the next high in the following order: the orientation levels of use(level 1; 20.9%), the refinement levels(level 5; 17.1%), the non-use levels(level 0; 15.0%), the preparation levels(level 2; 10.2%), the integration levels(level 6; 5.9%), the renewal levels(level 7; 4.8%), the routine levels(level 4; 4.8%). Third, for the innovation configuration of HE teachers on creativity and personality education, more than half of the HE teachers(56.1%) mainly focused on personality education in their HE classes; 31.0% of the HE teachers performed both creativity and personality education; a small number of teachers(6.4%) focused on creativity education; the same number of teachers(6.4%) responded that they do not focus on neither of the two. Examining the level and type of performance HE teachers applied, the average score on the performance of creativity and personality education was 3.76 out of 5.00 and the mean of creativity component was 3.59 and of personality component was 3.94, higher than standard. For the creativity education, openness/sensitivity(3.97) education was performed most and the next most in the following order: problem-solving skill(3.79), curiosity/interest(3.73), critical thinking(3.63), problem-finding skill(3.61), originality(3.57), analogy(3.47), fluency/adaptability(3.46), precision(3.46), imagination(3.37), and focus/sympathy(3.37). For the personality education, the following components were performed in order from most to least: power of execution(4.07), cooperation/consideration/just(4.06), self-management skill(4.04), civic consciousness(4.04), career development ability(4.03), environment adaptability(3.95), responsibility/ownership(3.94), decision making(3.89), trust/honesty/promise(3.88), autonomy(3.86), and global competency(3.55). Regarding what makes performing creativity and personality education difficult, most HE teachers(64.71%) chose the lack of instructional materials and 40.11% of participants chose the lack of seminar and workshop opportunity. 38.5% chose the difficulty of developing an evaluation criteria or an evaluation tool while 25.67% responded that they do not know any means of performing creativity and personality education. Regarding the better way to support for creativity and personality education, the HE teachers chose in order from most to least: 'expansion of hands-on activities for students related to education on creativity and personality'(4.34), 'development of HE classroom culture putting emphasis on creativity and personality'(4.29), 'a proper curriculum on creativity and personality education that goes along with students' developmental stages'(4.27), 'securing enough human resource and number of professors who will conduct creativity and personality education'(4.21), 'establishment of the concept and value of the education on creativity and personality'(4.09), and 'educational promotion on creativity and personality education supported by local communities and companies'(3.94).