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Gwangju, South Korea

Song C.H.,Chosun University | Song C.H.,JB Stem Cell Institute Inc. | Kim Y.G.,Chosun University
Tissue Engineering and Regenerative Medicine | Year: 2010

The selection of dominant human umbilical cord blood-derived mesenchymal stem cells (CHUCBMSCs) is a prerequisite for cell survival and also a key factor for avoiding senescence in MSCs as potential therapeutic agents in regenerative medicine. To facilitate this selection, we devised a novel Stem Cell Scoring System (SCSS) based on multi-lineage differentiation, growth rate and morphology analysis, cell cycle passaging, immunophenotypic analysis in combination with the evaluation of senescence-associated gene expression, reactive oxygen species formation and the effects of siRNA against senescence-associated genes including SA-β-Gal. The high scoring dominant cells (Group A; score 7∼10) survived 16 passages, compared to 12 passages for the low scoring group (Group C; score 1∼4). The percentage of lineages able to differentiate in vitro into osteogenic, adipogenic and neurogenic lineages were approximately 93.5%, 67.5% and 4.2% for high scoring cells, respectively. The differentiation capabilities of all lineages decreased with increasing passages, and the differentiation of the adipogenic and osteogenic lineages decreased more than that of the neurogenic lineage. A quantification of cell cycle inhibitor expression in MSCs showed that senescence is accompanied by increased expression of p21 and MMP1 (as indicated by lower SCSS), but not TRF1. Low scoring cells showed increased SA-β-gal staining and produced more ROS compared to high scoring cells. The scores of siRNA transfected cells increased, as expected; expression was more inhibited in high scoring cells than in low scoring cells. These findings suggest that hUCB-MSCs with high SCSS scores may be useful in regeneration processes or in transplantation therapies. Source

Lee S.H.,Chonnam National University | Lee Y.J.,Chonnam National University | Song C.H.,JB Stem Cell Institute Inc. | Ahn Y.K.,Chonnam National University | Han H.J.,Chonnam National University
American Journal of Physiology - Cell Physiology | Year: 2010

Here we show that the effect of hypoxia on human umbilical cord blood mesenchymal stem cell (hMSC) migration is via the modulation of focal adhesion kinase (FAK) and its related signaling pathways. Hypoxia increased hMSC migration and cell viability, whereas lactate dehydrogenase (LDH) release was not affected for up to 48 h (data not shown). In addition, hypoxia increased the level of reactive oxygen species (ROS) generation in a time-dependent manner. Hypoxia-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) were inhibited by the antioxidant (N-acetylcysteine, NAC, 10 -6 M) and (taurine, 4×10-6 M). Hypoxia-induced endothelial nitric oxide synthase (eNOS) phosphorylation was regulated by p38 MAPK and SAPK/JNK activation. In addition, hypoxia increased the level of hypoxia inducible factor (HIF)-1α expression, which was blocked by inhibition of eNOS. Also, hypoxia-induced expression of Flk-1, vascular endothelial growth factor (VEGF), and its secreted form were inhibited by HIF-1α small interfering RNA (siRNA). In this hypoxic condition, FAK and Src phosphorylation were increased in a time-dependent manner. Inhibition of Src with specific inhibitor (PP2, 10-8 M) blocked hypoxia-induced FAK activation. Subsequently, hypoxia-induced FAK phosphorylation was blocked by VEGF siRNA. Finally, hypoxia-induced increase of hMSC migration was inhibited by FAK siRNA. The results indicate that hypoxia increases migration of hMSCs via VEGF-mediated FAK phospholylation and involves the cooperative activity of the ROS, MAPK, eNOS and HIF-1α pathways. Copyright © 2010 the American Physiological Society. Source

Kim Y.S.,Chonnam National University | Kwon J.S.,Chonnam National University | Hong M.H.,Chonnam National University | Kim J.,JB Stem Cell Institute Inc. | And 6 more authors.
Artificial Organs | Year: 2010

Recent studies show that oxytocin has various effects on cellular behaviors. Oxytocin is reported to stimulate cardiomyogenesis of embryonic stem cells and endothelial cell proliferation. Mesenchymal stem cells (MSCs) are widely used for cardiac repair, and we elucidated the effect of oxytocin on umbilical cord derived-MSCs (UCB-MSCs). UCB-MSCs were pretreated with oxytocin (100 nM) and washed with saline prior to experiments. To evaluate their angiogenic potential and migration activity, tube formation assay and Boyden chamber assay were performed. For in vivo study, ischemia-reperfusion was induced in rats, and UCB-MSCs with or without oxytocin pretreatment were injected into the infarcted myocardium to evaluate the engraftment of injected cells. Histological and hemodynamic studies were performed. Oxytocin-treated UCB-MSCs showed a decrease in tube formation but a drastic increase in transwell migration activity. The transcription level of matrix metalloproteinase (MMP)-2 was increased in oxytocin-treated UCB-MSCs. Knock-down of MMP-2 by use of siRNA restored the tube formation, while reducing transmigration activity. In rats injected with oxytocin-treated UCB-MSCs, cardiac fibrosis and CD68 infiltration in the peri-infarct zone were reduced, whereas cell engraftment and connexin43 expression were greater than in rats injected with untreated UCB-MSCs. By contrast, angiogenesis did not differ significantly between the two groups. Cardiac contractility was higher in the group injected with oxytocin-treated UCB-MSCs than in the group injected with phosphate-buffered saline alone. Collectively, oxytocin is an effective priming reagent for stem cells for application to damaged heart tissue. © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Source

Choi H.S.,Korea Brain Research Institute | Kim H.J.,Korea Brain Research Institute | Oh J.-H.,Gachon University | Park H.-G.,JB Stem Cell Institute Inc. | And 5 more authors.
Neurobiology of Aging | Year: 2015

The treatment of Parkinson's disease (PD) using stem cells has long been the focus of many researchers, but the ideal therapeutic strategy has not yet been developed. The consistency and high reliability of the experimental results confirmed by animal models are considered to be a critical factor in the stability of stem cell transplantation for PD. Therefore, the aim of this study was to investigate the preventive and therapeutic potential of human adipose-derived stem cells (hASC) for PD and was to identify the related factors to this therapeutic effect. The hASC were intravenously injected into the tail vein of a PD mouse model induced by 6-hydroxydopamine. Consequently, the behavioral performances were significantly improved at 3 weeks after the injection of hASC. Additionally, dopaminergic neurons were rescued, the number of structure-modified mitochondria was decreased, and mitochondrial complex I activity was restored in the brains of the hASC-injected PD mouse model. Overall, this study underscores that intravenously transplanted hASC may have therapeutic potential for PD by recovering mitochondrial functions. © 2015 The Authors. Source

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