• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.38 no.6
• /
• pp.343-353
• /
• 2012

Objectives: This aim of this study was to effectively isolate mesenchymal stem cells (hSMSCs) from human submandibular skin tissues (termed hSMSCs) and evaluate their characteristics. These hSMSCs were then chemically induced to the neuronal lineage and analyzed for their neurogenic characteristics in vitro. Materials and Methods: Submandibular skin tissues were harvested from four adult patients and cultured in stem cell media. Isolated hSMSCs were evaluated for their multipotency and other stem cell characteristics. These cells were differentiated into neuronal cells with a chemical induction protocol. During the neuronal induction of hSMSCs, morphological changes and the expression of neuron-specific proteins (by fluorescence-activated cell sorting [FACS]) were evaluated. Results: The hSMSCs showed plate-adherence, fibroblast-like growth, expression of the stem-cell transcription factors Oct 4 and Nanog, and positive staining for mesenchymal stem cell (MSC) marker proteins (CD29, CD44, CD90, CD105, and vimentin) and a neural precursor marker (nestin). Moreover, the hSMSCs in this study were successfully differentiated into multiple mesenchymal lineages, including osteocytes, adipocytes, and chondrocytes. Neuron-like cell morphology and various neural markers were highly visible six hours after the neuronal induction of hSMSCs, but their neuron-like characteristics disappeared over time (24-48 hrs). Interestingly, when the chemical induction medium was changed to Dulbecco's Modified Eagle Medium (DMEM) supplemented with fetal bovine serum (FBS), the differentiated cells returned to their hSMSC morphology, and their cell number increased. These results indicate that chemically induced neuron-like cells should not be considered true nerve cells. Conclusion: Isolated hSMSCs have MSC characteristics and express a neural precursor marker, suggesting that human skin is a source of stem cells. However, the in vitro chemical neuronal induction of hSMSC does not produce long-lasting nerve cells and more studies are required before their use in nerve-tissue transplants.

• Biomolecules & Therapeutics
• /
• v.24 no.2
• /
• pp.132-139
• /
• 2016

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

• Archives of Plastic Surgery
• /
• v.35 no.1
• /
• pp.13-19
• /
• 2008

Purpose: Human adipose tissue-derived mesenchymal stem cells(hATSCs) can be differentiated into multiple mesenchymal lineages, including bone, cartilage, and muscle. And growth hormone play important roles in the normal growth and development of the CNS. In this study, we explored whether the transplanted hATSCs and growth hormones could improve functional recoveries from rats with contusive spinal cord injury. Methods: We divided 30 female rats, which were subjected to a weight driven implant spinal cord injury, into 3 groups with 10 rats each; Group A as a control group, group B with hATSCs transplantation on injured region, and group C with hATSCs transplantation and GH administration for 7 days. Then, we researched their neurologic functional recoveries before and 2, 4, and 8 weeks after transplantation using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. And we checked Y-chromosome positive cells by FISH(Fluorescent in situ hybridization) to identify the survival of transplanted mesenchymal stem cells. Results: After 4 weeks of transplantation, the group B and group C showed significant improvement of neurologic function on BBB locomotor rating scale in comparison with the group A(Group A: $13.1{\pm}0.58$, Group B: $14.6{\pm}0.69$, Group C: $14.9{\pm}0.56$). Moreover, the group C displayed meaningful recovery of neurologic function after 8 weeks in comparison with group B (Group B: $15.7{\pm}0.63$, Group C: $16.5{\pm}1.14$). The group A, the control one, improved for 5 weeks after injury, and had no more recovery. On the other hand, Group B and C showed the improvement of neurologic function continuously for 9 weeks after injury. Conclusion: In this study, we found out that hATSCs transplantation have an effect on neurologic functional recovery of spinal cord injured rat and GH injection seems to bring the synergistic results on this good tendency.

• Journal of Applied Biological Chemistry
• /
• v.58 no.3
• /
• pp.219-226
• /
• 2015

The anticancer activity of a methanolic extract from lemon leaves (MLL) was assessed in MCF-7-SC human breast cancer stem cells. MLL induced apoptosis in MCF-7-SC, as evidenced by increased apoptotic body formation, sub-G1 cell population, annexin V-positive cells, Bax/Bcl-2 ratio, as well as proteolytic activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Concomitantly, MLL induced the formation of acidic vesicular organelles, increased LC3-II accumulation, and reduced the activation of Akt, mTOR, and p70S6K, suggesting that MLL initiates an autophagic progression in MCF-7-SC via the Akt/mTOR pathway. Epithelial-mesenchymal transition (EMT), a critical step in the acquisition of the metastatic state, is an attractive target for therapeutic interventions directed against tumor metastasis. At low concentrations, MLL induced anti-metastatic effects on MCF-7-SC by inhibiting the EMT process. Exposure to MLL also led to an increase in the epithelial marker E-cadherin, but decreased protein levels of the mesenchymal markers Snail and Slug. Collectively, this study provides evidence that lemon leaves possess cytotoxicity and anti-metastatic properties. Therefore, MLL may prove to be beneficial as a medicinal plant for alternative novel anticancer drugs and nutraceutical products.

• Journal of Life Science
• /
• v.21 no.2
• /
• pp.286-291
• /
• 2011

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF-$1{\alpha}$ was induced by cobalt chloride (500 ${\mu}M$) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ${\mu}M$) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ${\mu}M$) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased ${\alpha}$-SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 ${\mu}M$ cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin ${\beta}3$ expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin ${\beta}3$-induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.

• 한국생물공학회:학술대회논문집
• /
• 2003.10a
• /
• pp.118-118
• /
• 2003

• 대한생식의학회:학술대회논문집
• /
• 2005.11a
• /
• pp.87-88
• /
• 2005

• 대한두경부종양학회:학술대회논문집
• /
• 1986.11a
• /
• pp.6.2-8
• /
• 1986

• 대한약리학회:학술대회논문집
• /
• 2006.10a
• /
• pp.103.2-103.2
• /
• 2006

• The Korean Journal of Food And Nutrition
• /
• v.24 no.4
• /
• pp.803-807
• /
• 2011

Human umbilical Mesenchymal Stem Cell(uMSC) has been known as one of major component to regenerate connective tissues such as bone, cartilage, fat and others. The effect of low(5%), normotensive(20%) oxygen and freezing-thawing damage on proliferation of uMSC were investigated. low oxygen concentration culture of uMSC resulted in enhanced proliferation significantly($p$ <0.05) than 20% of oxygen culture. After the freezing-thawing injury to uMSC, 5% oxygen culture showed marked proliferation of uMSC than that of 20% oxygen($p$ <0.05) in the 5th passage of uMSC. Expression of antioxidant enzymes such as superoxide anion 1 and glutathione peroxidase 1 appeared marked in 20% oxygen cultured uMSC, which suggest oxidative stress could induce less proliferation of uMSC. Above findings would suggest proliferation of uMSC in 5% of oxygen will give more yields.