• Molecules and Cells
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• v.24 no.3
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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.

• BMB Reports
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• v.49 no.2
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• pp.122-127
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• 2016

Engineered bone tissue is thought to be the ideal alternative for bone grafts in the treatment of related bone diseases. BMP9 has been demonstrated as one of the most osteogenic factors, and enhancement of BMP9-induced osteogenesis will greatly accelerate the development of bone tissue engineering. Here, we investigated the effect of insulin-like growth factor 1 (IGF1) on BMP9-induced osteogenic differentiation, and unveiled a possible molecular mechanism underling this process. We found that IGF1 and BMP9 are both detectable in mesenchymal stem cells (MSCs). Exogenous expression of IGF1 potentiates BMP9-induced alkaline phosphatase (ALP), matrix mineralization, and ectopic bone formation. Similarly, IGF1 enhances BMP9-induced endochondral ossification. Mechanistically, we found that IGF1 increases BMP9-induced activation of BMP/Smad signaling in MSCs. Our findings demonstrate that IGF1 can enhance BMP9-induced osteogenic differentiation in MSCs, and that this effect may be mediated by the enhancement of the BMP/Smad signaling transduction triggered by BMP9.

• Development and Reproduction
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• v.20 no.2
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• pp.141-147
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• 2016

Rad51 is a key component of homologous recombination (HR) to repair DNA double-strand breaks and it forms Rad51 recombinase filaments of broken single-stranded DNA to promote HR. In addition to its role in DNA repair and cell cycle progression, Rad51 contributes to the reprogramming process during the generation of induced pluripotent stem cells. In light of this, we performed reprogramming experiments to examine the effect of co-expression of Rad51 and four reprogramming factors, Oct4, Sox2, Klf4, and c-Myc, on the reprogramming efficiency. Co-expression of Rad51 significantly increased the numbers of alkaline phosphatase-positive colonies and embryonic stem cell-like colonies during the process of reprogramming. Co-expression ofRad51 significantly increased the expression of epithelial markers at an early stage of reprogramming compared with control cells. Phosphorylated histone H2AX (${\gamma}H2AX$), which initiates the DNA double-strand break repair system, was highly accumulated in reprogramming intermediates upon co-expression of Rad51. This study identified a novel role of Rad51 in enhancing the reprogramming efficiency, possibly by facilitating mesenchymal-to-epithelial transition and by regulating a DNA damage repair pathway during the early phase of the reprogramming process.

• Molecules and Cells
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• v.37 no.1
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• pp.17-23
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• 2014

We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or ${\beta}$-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. We demonstrated that Sp1 protein or mRNA expression is induced by Bcl-w using Western blotting or RT-PCR, respectively, and markedly elevated in high-grade glioma specimens compared with low-grade glioma tissues using tissue array. However, relationship between Bcl-w-related signaling and aggressive characteristic of GBM is poorly characterized. This study suggested that Bcl-w-induced Sp1 activation promoted expression of glioma stem-like cell markers, such as Musashi, Nanog, Oct4 and sox-2, as well as neurosphere formation and invasiveness, using western blotting, neurosphere formation assay, or invasion assay, culminating in their aggressive behavior. Therefore, Bcl-w-induced Sp1 activation is proposed as a putative marker for aggressiveness of GBM.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.3
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• pp.268-272
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• 2021

Bone marrow-derived cell (BMDC) therapy has numerous applications as potential biological cells for use in regenerative medicine. Here, we present an original case of endometrial atrophy associated with genital tuberculosis in a woman who achieved a live birth with BMDC. This 27-year-old woman came to our center with endometrial atrophy and primary infertility. She had a past history of genital tuberculosis and amenorrhea. Her husband's semen quality was normal. The patient was counseled for hysteroscopy due to thin endometrium and advised in vitro fertilization (IVF) with donor eggs in lieu of poor ovarian reserve. Several attempts of IVF with hormone replacement therapy (HRT) were made, but the desired thickness of the endometrium was not achieved. Uterine artery injection of BMDC through interventional radiology was given, followed by HRT for three months, which resulted in improved endometrium. This was subsequently followed by IVF with donor egg. The treatment resulted in the conception and delivery of a 3.1-kg baby boy through lower segment caesarean section with no antenatal, intranatal or postnatal complications. Recently, there has been massive interest in stem cells as a novel treatment method for regenerative medicine, and more specifically for the regeneration of human endometrium disorders like Asherman syndrome and thin endometrium, which was the reason behind using this strategy for treatment.

• Journal of Life Science
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• v.23 no.1
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• pp.131-136
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• 2013

Sirtuin proteins have emerged as important modulators of several age-associated diseases. These include cancer and diabetes, as well as cardiovascular and neurodegenerative diseases. Among the sirtuin family members, SIRT2 mRNA is strongly expressed. To investigate the pathophysiological significance of SIRT2 as a primary regulator of angiogenesis, we focused on the biological role of SIRT2 under hypoxic conditions, examining the gene expression pattern of sirtuin family members in human umbilical vein endothelial cells (HUVECs). SIRT2 was expressed primarily in the cytoplasm, but it was dynamically trans-localized in the nuclear by hypoxia stimuli. Interestingly, both SIRT2 and the pro-angiogenic factor, VEGF, were up- regulated by hypoxia. A Matrigel assay demonstrated that the HUVECs formed a tube-like structure under hypoxia. The SIRT2 inhibitor, AK-1, significantly decreased the tube-forming activity of the HUVECs under either normoxia or hypoxia conditions. These findings suggest that SIRT2 might be a key regulator of angiogenesis.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.4
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• pp.293-298
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• 2003

목 적: 인간의 배아줄기세포는 전분화능과 영속성을 가지고 있어 발생 및 분화에 관련된 기초 연구 뿐 만 아니라 재생의학, 약물검색 등에서도 매우 유용한 재료로 이용될 수 있다.본 연구에서는 유전체의 변형이 배아줄기세포주의 확립 효율에 미치는 영향을 살펴보고자 비정상적인 포배기 배아에서 내세포괴를 분리하여 배양하였다. 연구 방법: 인간의 체외수정 및 배아이식술에서 공여 받은1개 또는3개의 전핵이 관찰되는 비정상 수정란 (n=20)과 착상전 유전진단에서 이수성이 확인된 배아 (n=27)를 대상으로 하였다. 일반적인 immunosurgery 방법으로 영양배엽세포들을 제거하고 내세포괴를 분리한 후 PMEF 혹은 STO feeder 세포위에서 배양하였다. 배아줄기세포의 배양시스템을 검증하기 위해서 이미 확립된 Miz-hES1 cell line을 동시에 같은 조건 하에서 계대배양하였다. 결 과: 비정상 수정란에서 발생된 포배기 배아에서 분리한 1개의 내세포괴가 배아줄기세포와 유사한 colony를 형성하였으나, 계대배양에는 실패하였다. 이수성 배아에서 발생된 포배기 배아의 내세포괴 배양에서는 두개의 colony가 계대배양 중에 영양배엽세포의 형태로 분화되어 미분화 상태를 유지하지 못하였다. 동일한 시기와 조건 하에서 계대배양된 Miz-hES1 cell line이 미분화상태로 유지됨을 karyotyping (46, XY)과 immunophenotyping (positive in SSEA-3 and -4)으로 확인하였다. 결 론: 본 연구의 결과에서 비정상 수정란과 이수성 배아에서 발생된 포배기 배아에서 유래한 내세포괴는 배아줄기세포주 확립 및 미분화 상태 유지 능력이 매우 저조한 것으로 여겨진다. 따라서, 인간의 배아줄기세포주를 확립하는데 있어 배아의 정상여부가 중요한 요소로 작용할 것으로 생각된다.

• Journal of Life Science
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• v.21 no.5
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• pp.631-646
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• 2011

Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

• Molecules and Cells
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• v.19 no.3
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• pp.342-349
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• 2005

Cytokinins are adenine derivatives that regulate numerous plant growth and developmental processes, including apical and floral meristem development, stem growth, leaf senescence, apical dominance, and stress tolerance. However, not much is known about how cytokinin biosynthesis and metabolism is regulated. We identified a novel Arabidopsis gene, ALL, encoding an aldolase-like enzyme that regulates cytokinin signaling. An Arabidopsis mutant, all-1D, in which ALL is activated by the nearby insertion of the 35S enhancer, exhibited extreme dwarfism with rolled, dark-green leaves and reduced apical dominance, symptomatic of cytokinin-overproducing mutants. Consistent with this, ARR4 and ARR5, two representative primary cytokinin-responsive genes, were significantly induced in all-1D. Whereas SHOOT MERISTEMLESS (STM) and KNAT1, which regulate meristem development, were also greatly induced, expression of REV and PHV that regulate lateral organ polarity was inhibited. ALL encodes an aldolase-like enzyme that belongs to the HpcH/HpaI aldolase family in prokaryotes and is down-regulated by exogenous cytokinin, possibly through a negative feedback pathway. We propose that ALL is involved in cytokinin biosynthesis or metabolism and acts as a positive regulator of cytokinin signaling during shoot apical meristem development and determination of lateral organ polarity.

• Journal of Plant Biotechnology
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• v.49 no.3
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• pp.171-177
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• 2022

The precise homeostatic regulation of local auxin accumulation in xylem precursors of cambium stem cell tissues is one of the most important mechanisms for plant vascular patterning and radial secondary growth. Walls are thin (WAT1), a novel intracellular auxin transporter, contributes directly to the auxin accumulation maxima in xylem precursors. According to recent research, the auxin signaling activated pathway-related gene network was significantly enriched during the secondary growth of Panax ginseng storage roots. These imply that during P. ginseng root secondary growth, specific signaling mechanisms for local auxin maxima in the vascular cambial cells are probably triggered. This study identified four WAT1-like genes, PgWAT1-1/-2 and PgWAT2-1/-2, in the P. ginseng genome. Their expression levels were greatly increased in nitratetreated storage roots stimulated for secondary root growth. PgWAT1-1 and PgWAT2-1 were similar to WAT1 from Arabidopsis and tomato plants in terms of their subcellular localization at a tonoplast and predicted transmembrane topology. We discovered that overexpression of PgWAT1-1 and PgWAT2-1 was sufficient to compensate for the secondary growth defects observed in slwat1-copi loss of function tomato mutants. This critical information from the PgWAT1-1 and PgWAT2-1 genes can potentially be used in future P. ginseng genetic engineering and breeding for increased crop yield.