• Development and Reproduction
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• v.11 no.3
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• pp.235-243
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• 2007

Human umbilical cord blood(HUCB) contains a rich source of hematopoietic stem cells, mesenchymal stem cells and endothelial cell precursors. Mesenchymal stem cells(MSCs) in HUCB are multipotent stem cells, differ from hematopoietic stem cells and can be differentiated into neural cells. We studied on transdifferentiation-promoting conditions in neural cells and cholinergic neuron induction of HUCB-derived MSCs. Neural differentiation was induced by addingdimethyl sulphoxide(DMSO) and butylated hydroxyanisole(BHA) in Dulbeco's Modified Essential Medium(DMEM) and fetal bovine serum(FBS). Differentiation of MSCs to cholinergic neurons was induced by combined treatment with basic fibroblast growth factor(bFGF), retinoic acid(RA) and sonic hedgehog(Shh). MSCs treated with DMSO and BHA rapidly assumed the morphology of multipolar neurons. Both immunocytochemistry and RT-PCR analysis indicated that the expression of a number of neural markers including $\beta$-tubulin III, GFAP and MBP, was markedly elevated during this acute differentiation. The differentiation rate was about $32.3{\pm}2.9%$ for $\beta$-tubulin III-positive cells, $11.0{\pm}0.9%$ for GFAP, and $9.4{\pm}1.0%$ for Gal-C. HUCB-MSCs treated combinatorially with bFGF, RA and Shh were differentiated into cholinergic neurons. After cholinergic neuronal differentiation, the $\beta$-tubulin III-positive cell population of total cells was $31.3{\pm}3.2%$ and of differentiated neuronal population, $70.0{\pm}7.8%$ was ChAT-positive showing 3 folds higher in cholinergic population than neural induction. Conclusively, HUCB-derived MSCs can be differentiated into neural and cholinergic neurons and these findings suggest that HUCB are alternative cell source of treatment for neurodegenerative diseases such as Alzheimer's disease.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.4
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• pp.205-212
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• 2009

Purpose : The purpose of this study was to examine the expression of various angiogenic factors during osteoblastic differentiation of periostealderived cells and the effects of osteogenic inductive medium of periosteal-derived cells on the proliferation of endothelial progenitor cells. Materials and methods : Periosteal-derived cells were obtained from mandibular periosteums and introduced into the cell culture. After passage 3, the cells were divided into two groups and cultured for 21 days. In one group, the cells were cultured in the DMEM supplemented with osteogenic inductive agent, including 50g/ml L-ascorbic acid 2-phosphate, 10 nM dexamethasone and 10 mM -glycerophosphate. In the other group, they were cultured in DMEM supplemented without osteogenic inductive agent. VEGF isoforms, VEGFR-1, VEGFR-2, and neuropilin-1 mRNA expression was observed. Human umbilical cord blood-derived endothelial progenitor cell proliferation was also observed. Results : The expression of VEGF isoforms was higher in osteogenic inductive medium than in non-osteogenic inductive medium. The expression of VEGFR-2 was also higher in osteogenic inductive medium than in non-osteogenic inductive medium. However, the expression of VEGFR-1 and neuropilin-1 was similar in both osteogenic inductive medium and non-osteogenic inductive medium. In addition, conditioned medium from differentiated periosteal-derived cells stimulated human umbilical cord blood-derived endothelial progenitor cell numbers compared to conditioned medium from non-differentiated periosteal-derived cells. Conclusion : These results suggest that in vitro osteoblastic differentiation of periosteal-derived cells has angiogenic capacity to support endothelial progenitor cell numbers.

• BMB Reports
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• v.52 no.5
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• pp.318-323
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• 2019

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possesses uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated $CD4^+$ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-${\gamma}$ ($IFN-{\gamma}$). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, $IFN-{\gamma}$-mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

• Archives of Plastic Surgery
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• v.36 no.5
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• pp.519-524
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• 2009

Purpose: This study was conducted to establish the most effective method of cell therapy by comparing and analyzing the level of wound healing after various cell delivery methods. Methods: Human mesenchymal stem cells were administered using 5 different methods on full thickness skin defects which were deliberately created on the back of 4 - week old mice using a 8 mm punch. Different modes of administration, cell suspension, local injection, collagen GAG matrix seeding, fibrin, and hydrogel mix methods were used. In each experiment group, $4{\times}105$ mesenchymal stem cells were administered according to 5 deferent methods, and were not for the corresponding control group. Results: The wound healing rate was fastest in the local injection group. The wound healing rate was relatively slow in the collagen matrix group, however, the number of blood vessels or VEGF increased most in this group. Conclusion: For rapid wound healing through wound contraction, it is advantageous to administer MSC by the local injection method. For the healing process of a wide area, such as a burn, the seeding of cells to collagen matrix is thought to be effective.

• Journal of Microbiology and Biotechnology
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• v.12 no.3
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• pp.483-489
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• 2002

The role of $G{\alpha}12\;and\;G{\alpha}13$ in modulating the IgE receptor-mediated histamine secretion in the streptolysin-o-permeabilized human cultured mast cell was investigated. The expression of $G{\alpha}12\;and\;G{\alpha}13$ proteins were regulated during human cultured mast cell differentiation, and a significant correlation was observed between the levels of expression of $G{\alpha}12\;and\;G{\alpha}13$ proteins and IgE receptor-mediated histamine secretion capability in human cultured mast cells. Antibodies against $G{\alpha}12\;and\;G{\alpha}13$ effectively inhibited the IgE receptor-induced histamine release, and the concentration of anti-$G{\alpha}12$ antibody used to inhibit histamine secretion was shown to also inhibit the IgE receptor-mediated elevation of intracellular $Ca^2+$. Therefore, the results suggest that $G{\alpha}12\;and\;G{\alpha}13$ play roles in modulating IgE receptor-activated $Ca^2+$ influx, thereby regulating histamine release in cultured human mast cells. This is the first report to show that $G{\alpha}12\;and\;G{\alpha}13$ are involved in the regulation of $Ca^2+$ mediated exocytosis in human cultured mast cells.

• Molecules and Cells
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• v.45 no.6
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• pp.403-412
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• 2022

Hypoxia leads to significant cellular stress that has diverse pathological consequences such as cardiovascular diseases and cancers. MicroRNAs (miRNAs) are one of regulators of the adaptive pathway in hypoxia. We identified a hypoxia-induced miRNA, miR-34c, that was significantly upregulated in hypoxic human umbilical cord vein endothelial cells (HUVECs) and in murine blood vessels on day 3 of hindlimb ischemia (HLI). miR-34c directly inhibited BCL2 expression, acting as a toggle switch between apoptosis and autophagy in vitro and in vivo. BCL2 repression by miR-34c activated autophagy, which was evaluated by the expression of LC3-II. Overexpression of miR-34c inhibited apoptosis in HUVEC as well as in a murine model of HLI, and increased cell viability in HUVEC. Importantly, the number of viable cells in the blood vessels following HLI was increased by miR-34c overexpression. Collectively, our findings show that miR-34c plays a protective role in hypoxia, suggesting a novel therapeutic target for hypoxic and ischemic diseases in the blood vessels.

• The Korean Journal of Food And Nutrition
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• v.22 no.2
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• pp.313-319
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• 2009

To improve the growth of human mesenchymal stem cells(hMSCs) under general cell culture conditions(20% $O_2$ and 5% $CO_2$), we examined the effect of s-allylcysteine(SAC), which is known as an antioxidant and the main component of aged-garlic extract, on hydrogen peroxide-induced cellular stress in hMSCs. We found that SAC blocked hydrogen peroxideinduced cell death and cellular apoptosis, but that SAC did not improve the growth of hMSCs during short-term culture. To evaluate the protective effect of SAC, we examined the endogenous expression of the antioxidant enzymes catalase (CAT), superoxide dismutase(SOD), and glutathione peroxidase(Gpx) in hMSCs. Hydrogen peroxide was found to downregulate the expression of CAT, SOD, and Gpx at the protein level. However, in the pre-treatment group of SAC, SAC inhibited the hydrogen peroxide-induced down-regulation of CAT, SOD, and Gpx. Unfortunately, treatment with SAC alone did not induce the up-regulation of antioxidant enzymes and the cell proliferation of hMSCs. Surprisingly, SAC improved cell growth in a single cell level culture of hMSCs. These results indicate that SAC may be involved in the preservation of the self-renewal capacity of hMSCs. Taken together, SAC improves the proliferation of hMSCs via inhibition of oxidative-stress-induced cell apoptosis through regulation of antioxidant enzymes. In conclusion, SAC may be an indispensable component in an in vitro culture system of human MSCs for maintaining self-renewal and multipotent characterization of human MSCs.

• Molecules and Cells
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• v.44 no.8
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• pp.580-590
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• 2021

Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma. Here, we examined the effect of human umbilical cord blood-derived MSCs (hUC-MSC) on two mouse models of severe asthma, namely, Alternaria alternata-induced and house dust mite (HDM)/diesel exhaust particle (DEP)-induced asthma. hUC-MSC treatment attenuated lung type 2 (Th2 and type 2 innate lymphoid cell) inflammation in both models. However, these effects were only observed with particular treatment routes and timings. In vitro co-culture showed that hUC-MSC directly downregulated the interleukin (IL)-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells from asthma patients. Thus, these results showed that hUC-MSC treatment can ameliorate asthma by suppressing the asthmogenic cytokine production of effector cells. However, the successful clinical application of MSCs in the future is likely to require careful optimization of the route, dosage, and timing.

• Clinical and Experimental Pediatrics
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• v.50 no.12
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• pp.1194-1199
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• 2007

Purpose : It was generally accepted now a days that the pathogenesis of preeclampsia, small for gestational age (SGA), intrauterine growth retardation and fetal origin of adult diseases were related with a endothelial cell dysfunction. The purpose of this study was to know the relation of such diseases by assessing the level of endothelin-1. Methods : SGA babies, newborns of preeclampsia and normal control mother were included in this study. Isolated endothelial cells were centrifugated and mixed with media in $37^{\circ}C$, 5% $CO_2$ to obtain confluent monolayer of cultured human umbilical venous endothelial cell (HUVEC). Endothelin-1 levels were determined by Endothelin-1 colorimetric (EIA) Kits. We examined the endothelin-1 level in the HUVEC supernatants from SGA baby, and newborns from preeclampsia as well as normal mother. Also, we compared the endothelin-1 level of cultured normal HUVEC incubated with serum from cord blood of SGA, babies of preeclampsia or normal control mother. Results : The endothelin-1 levels in cultured HUVEC supernatants of three groups showed no significant difference but the endothelin-1 levels of cultured normal HUVEC incubated with serum from preeclampsia mother or SGA mother was significantly higher than those from newborns of control mothers (P<0.05). Conclusion : These findings suggest that there may be the factor which affect the endothelin-1 level in serum of cord blood from SGA and preeclampsia.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.34-44
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• 2020

Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.