Publications (10)37.7 Total impact
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Article: Isolation and characterization of equine amniotic membrane-derived mesenchymal stem cells.
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ABSTRACT: Recent studies have shown that mesenchymal stem cells (MSCs) are able to differentiate into multi-lineage cells such as adipocytes, chondroblasts and osteoblasts. Amniotic membrane from whole placenta is a good source of stem cells in humans. The amniotic membrane has potential clinical applications in wound healing and corneal surface reconstruction. Moreover, it can be easily obtained after delivery, usually discarded as classified waste. In this study, we successfully isolated and characterized equine amniotic membrane-derived mesenchymal stem cells (eAM-MSCs), which were cultured and maintained in low-glucose Dulbecco's modified Eagle's medium. The proliferation of eAM-MSCs was measured based on the cumulative population doubling level (CPDL). Immunophenotyping of eAM-MSCs by flow cytometry showed that major population of mesenchymal origin. To confirm differentiation ability, a multi-lineage differentiation assay was conducted. We found that under appropriate conditions, eAM-MSCs are capable of multi-lineage differentiation. Our results indicate that eAM-MSCs may be a good source of stem cells like human amniotic membrane, making them potentially useful for veterinary regenerative medicine and cell therapy.Journal of veterinary science (Suwŏn-si, Korea) 02/2013; · 0.89 Impact Factor -
Article: Isolation and characterization of antler derivedmultipotent stem cells.
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ABSTRACT: Recent studies have reported that stem cells can be isolated from various tissues such as bone marrow, fatty tissue, umbilical cord blood, Wharton's jelly and placenta. These types of stem cell studies have also arisen in veterinary medicine. Deer antlers show a seasonal re-growth of tissue, an unusual feature in mammals. Antler tissue therefore might offer a source of stem cells. To explore the possibility of stem cell populations within deer antlers, we isolated and successfully cultured antler-derived multipotent stem cells (MSCs). Antler MSCs were maintained in growth medium, and proliferation potential was measured via an assay called the cumulative population doubling level. Immunophenotyping and immunostaining revealed the intrinsic characteristic stem cell markers of antler MSCs. To confirm the ability to differentiate, we conducted osteogenic, adipogenic and chondrogenic induction under the respective differentiation conditions. We discovered that antler MSCs have the ability to differentiate into multiple lineages. In conclusion, our results show that deer antler tissue may contain MSCs and therefore may be a potential source for veterinary regenerative therapeutics.Cell Transplantation 01/2013; · 5.13 Impact Factor -
Article: HMGA2 regulates the in vitro aging and proliferation of human umbilical cord blood-derived stromal cells through the mTOR/p70S6K signaling pathway.
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ABSTRACT: The human high-mobility group protein A2 (HMGA2) protein is an architectural transcription factor that transforms chromatin structure by binding to DNA. Recently, it has been reported that HMGA2 is highly expressed in fetal neural stem cells and has the capacity to promote stemness. However, there is currently no information available on the functional significance and molecular mechanisms of the cellular in vitro aging and proliferation of human umbilical cord blood-derived stromal cells (hUCBSCs). In the present study, we evaluated the direct effects of HMGA2 on the cellular aging and proliferation of hUCBSCs and investigated potential regulatory mechanisms responsible for the corresponding functions. We found that the overexpression of HMGA2 enhanced proliferation and reduced or even reversed the in vitro aging process of hUCBSCs. This effect was accompanied by the increased expression of cyclin E and CDC25A and the significantly decreased expression of cyclin-dependent kinase inhibitors. Furthermore, HMGA2 inhibition compromised cell proliferation and adipogenic differentiation in early-stage hUCBSCs. From the molecular/cellular functional analysis of microarray data, we found that HMGA2 overexpression induced a PI3K/Akt/mTOR/p70S6K cascade, which in turn suppressed the expression of p16(INK4A) and p21(CIP1/WAF1) in hUCBSCs. These results provide novel insights into the mechanism by which HMGA2 regulates the in vitro aging and proliferation of hUCBSCs.Stem cell research 11/2012; 10(2):156-165. · 3.39 Impact Factor -
Article: JNK Activation by Up-Regulation of iNOS on Cholesterol Accumulation Limits Neurogenesis and Induces Region-Specific DNA Damage Responses in the Subventricular Zone of NPC Mice.
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ABSTRACT: Abstract Aims: We explore the region-specific impact of nitric oxide (NO) on adult neural stem cell (aNSC) niches with regard to neurogenesis and NSC damage and investigate the underlying mechanisms in Niemann-Pick disease type C (NPC) mice. Results: Among the two anatomical stem-cell niches of the brain, subventricular zone (SVZ)-derived aNSCs enhanced c-Jun N-terminal kinase (JNK) activity because of excessive NO production by the cholesterol accumulation. Activated JNK interacts with γH2AX, a marker for DNA damage; however, almost none of the aNSCs in the dentate gyrus (DG) showed either JNK signaling activation or abundant DNA damage. SVZ-derived aNSCs were protected from DNA damage by the treatment of N(ω)-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor, both in vitro and in vivo. We also observed that U18666A, an inducer of cholesterol accumulation, increased inducible NOS expression, JNK activation, and DNA damage in the wild type (WT)-aNSCs. Interestingly, we found that endogenous cholesterol efflux transporters and their regulator were less activated in the SVZ than in the DG, in both WT and NPC mice. This result explains the high vulnerability of SVZ-derived aNSCs to the cholesterol imbalance as observed in NPC mice. Innovation and Conclusion: In this study, we demonstrated that the SVZ-derived aNSCs might be major targets of NPC. Significantly, aNSCs showed different responses depending on their anatomical origins due to dissimilarities in their cholesterol transporting system and NO-dependent JNK activation. These findings can contribute to the understanding of the region-specific nature of the two SVZ and DG neurogenic niches. Antioxid. Redox Signal. 00, 000-000.Antioxidants & Redox Signaling 03/2012; · 8.20 Impact Factor -
Article: Isolation and characterization of canine amniotic membrane-derived multipotent stem cells.
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ABSTRACT: Recent studies have shown that amniotic membrane tissue is a rich source of stem cells in humans. In clinical applications, the amniotic membrane tissue had therapeutic effects on wound healing and corneal surface reconstruction. Here, we successfully isolated and identified multipotent stem cells (MSCs) from canine amniotic membrane tissue. We cultured the canine amniotic membrane-derived multipotent stem cells (cAM-MSCs) in low glucose DMEM medium. cAM-MSCs have a fibroblast-like shape and adhere to tissue culture plastic. We characterized the immunophenotype of cAM-MSCs by flow cytometry and measured cell proliferation by the cumulative population doubling level (CPDL). We performed differentiation studies for the detection of trilineage multipotent ability, under the appropriate culture conditions. Taken together, our results show that cAM-MSCs could be a rich source of stem cells in dogs. Furthermore, cAM-MSCs may be useful as a cell therapy application for veterinary regenerative medicine.PLoS ONE 01/2012; 7(9):e44693. · 4.09 Impact Factor -
Article: The simplest method for in vitro β-cell production from human adult stem cells.
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ABSTRACT: Diabetes mellitus is a challenging autoimmune disease. Biomedical researchers are currently exploring efficient and effective ways to solve this challenge. The potential of stem cell therapies for treating diabetes represents one of the major focuses of current research on diabetes treatment. Here, we have attempted to differentiate adult stem cells from umbilical cord blood-derived mesenchymal cells (UCB-MSC), Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) and amniotic epithelial stem cells (AE-SC) into insulin-producing cells. The serum-free protocol developed in this study resulted in the differentiation of cells into definitive endoderm, pancreatic foregut, pancreatic endoderm and, finally, pancreatic endocrine cells, which expressed the marker genes SOX17, PDX1, NGN3, NKX6.1, INS, GCG, and PPY, respectively. Detection of the expression of the gap junction-related gene connexin-36 (CX36) using RT-PCR provided conclusive evidence for insulin-producing cell differentiation. In addition to this RT-PCR result, insulin and C-peptide protein were detected by immunohistochemistry and ELISA. Glucose stimulation test results showed that significantly greater amounts of C-peptide and insulin were released from differentiated cells than from undifferentiated cells. In conclusion, the methods investigated in this study can be considered an effective and efficient means of obtaining insulin-producing cells from adult stem cells within a week.Differentiation 07/2011; 82(3):144-52. · 2.81 Impact Factor -
Article: The regulatory role of c-MYC on HDAC2 and PcG expression in human multipotent stem cells.
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ABSTRACT: Myelocytomatosis oncogene (c-MYC) is a well-known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well-known chromosomal modification genes. The aim of this study was to elucidate the role of c-MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c-MYC expression was modified by gene knockdown and overexpression via lentivirus vector. Using the modified c-MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c-MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c-MYC knocked-down human umbilical cord blood-derived MSCs, whereas they were increased in c-MYC overexpressing cells. Similarly, RT-PCR and Western blotting results revealed that HDAC2 expression was decreased in c-MYC knocked-down and increased in c-MYC overexpressing hMSCs. Database indicates presence of c-MYC binding motif in HDAC2 promoter region, which was confirmed by chromatin immunoprecipitation assay. The influence of c-MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c-MYC over HDAC2 and PcG genes. c-MYCs' regulatory role over HDAC2 was also confirmed in human adipose tissue-derived MSCs and bone-marrow derived MSCs. From this finding, it can be concluded that c-MYC plays a vital role in cell proliferation and differentiation via chromosomal modification.Journal of Cellular and Molecular Medicine 07/2011; 15(7):1603-14. · 4.13 Impact Factor -
Article: DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs.
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ABSTRACT: Epigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16(INK4A) and p21(CIP1/WAF1) expression. DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16(INK4A) and p21(CIP1/WAF1) promoter regions. Enrichment of EZH2, the key factor that methylates histone H3 lysine 9 and 27 residues, was decreased on the p16(INK4A) and p21(CIP1/WAF1) promoter regions. We found that DNMT inhibition decreased expression levels of Polycomb-group (PcG) proteins and increased expression of microRNAs (miRNAs), which target PcG proteins. Decreased CpG island methylation and increased levels of active histone marks at genomic regions encoding miRNAs were observed after 5-AzaC treatment. Taken together, DNMTs have a critical role in regulating the cellular senescence of hUCB-MSCs through controlling not only the DNA methylation status but also active/inactive histone marks at genomic regions of PcG-targeting miRNAs and p16(INK4A) and p21(CIP1/WAF1) promoter regions.PLoS ONE 01/2011; 6(5):e19503. · 4.09 Impact Factor -
Article: Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood.
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ABSTRACT: Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are known to trigger an innate immune response against microbial infection. Although studies suggest that activation of TLRs modulate the function of mesenchymal stem cells (MSCs), little is known about the role of NLRs on the MSC function. In this study, we investigated whether NOD1 and NOD2 regulate the functions of human umbilical cord blood-derived MSCs (hUCB-MSCs). The genes of TLR2, TLR4, NOD1, and NOD2 were expressed in hUCB-MSCs. Stimulation with each agonist (Pam(3)CSK(4) for TLR2, LPS for TLR4, Tri-DAP for NOD1, and MDP for NOD2) led to IL-8 production in hUCB-MSC, suggesting the expressed receptors are functional in hUCB-MSC. CCK-8 assay revealed that none of agonist influenced proliferation of hUCB-MSCs. We next examined whether TLR and NLR agonists affect osteogenic-, adipogenic-, and chondrogenic differentiation of hUCB-MSCs. Pam(3)CSK(4) and Tri-DAP strongly enhanced osteogenic differentiation and ERK phosphorylation in hUCB-MSCs, and LPS and MDP also slightly did. Treatment of U0126 (MEK1/2 inhibitor) restored osteogenic differentiation enhanced by Pam(3)CSK(4). Tri-DAP and MDP inhibited adipogenic differentiation of hUCB-MSCs, but Pam(3)CSK(4) and LPS did not. On chondrogenic differentiation, all TLR and NLR agonists could promote chondrogenesis of hUCB-MSCs with difference in the ability. Our findings suggest that NOD1 and NOD2 as well as TLRs are involved in regulating the differentiation of MSCs.PLoS ONE 01/2010; 5(10):e15369. · 4.09 Impact Factor -
Article: Isolation and characterization of canine umbilical cord blood-derived mesenchymal stem cells.
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ABSTRACT: Vol. 10, No. 3, pp. 181-187, 2009. The sentence on 25th line of the left column in page 185 "The pellet formed aggregates in the bottom of the tube (Fig. 3D), and positive to toluidine blue staining (Figs. 4E and F)" should be corrected as following. --> The pellet formed aggregates in the bottom of the tube (Fig. 3D), and positive to toluidine blue staining (Figs. 3E and F).Journal of veterinary science (Suwŏn-si, Korea) 12/2009; 10(4):369. · 0.89 Impact Factor
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Institutions
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2009–2012
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Seoul National University
- College of Veterinary Medicine
Seoul, Seoul, South Korea
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