CoreStem Inc.

Seoul, South Korea

CoreStem Inc.

Seoul, South Korea
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Kim Y.S.,Hanyang University | Noh M.Y.,Hanyang University | Kim J.Y.,Hanyang University | Yu H.-J.,Bundang Jesaeng General Hospital | And 3 more authors.
Molecular Neurobiology | Year: 2013

Mesenchymal stromal cells (MSCs) are emerging as candidate cells for the treatment of neurological diseases because of their neural replacement, neuroprotective, and neurotrophic effects. However, the majority of MSCs transplanted by various routes fail to reach the site of injury, and they have demonstrated only minimal therapeutic benefit in clinical trials. Therefore, enhancing the migration of MSCs to target sites is essential for this therapeutic strategy to be effective. In this study, we assessed whether inhibition of glycogen synthase kinase-3β (GSK-3β) increases the migration capacity of MSCs during ex vivo expansion. Human bone marrow MSCs (hBM-MSCs) were cultured with various GSK-3β inhibitors (LiCl, SB-415286, and AR-A014418). Using a migration assay kit, we found that the motility of hBM-MSCs was significantly enhanced by GSK-3β inhibition. Western blot analysis revealed increased levels of migration-related signaling proteins such as phospho-GSK-3β, β-catenin, phospho-c-Raf, phospho-extracellular signal-regulated kinase (ERK), phospho-β-PAK-interacting exchange factor (PIX), and CXC chemokine receptor 4 (CXCR4). In addition, real-time polymerase chain reaction demonstrated increased expression of matrix metalloproteinase-2 (MMP-2), membrane-type MMP-1 (MT1-MMP), and β-PIX. In the reverse approach, treatment with β-PIX shRNA or CXCR4 inhibitor (AMD 3100) reduced hBM-MSC migration. These findings suggest that inhibition of GSK-3β during ex vivo expansion of hBM-MSCs may enhance their migration capacity by increasing expression of β-catenin, phospho-c-Raf, phospho-ERK, and β-PIX and the subsequent up-regulation of CXCR4. Enhancing the migration capacity of hBM-MSCs by treating these cells with GSK-3β inhibitors may increase their therapeutic potential. © 2013 Springer Science+Business Media New York.


Koh S.-H.,Hanyang University | Baik W.,Hanyang University | Noh M.Y.,Hanyang University | Cho G.W.,Hanyang University | And 3 more authors.
Experimental Neurology | Year: 2012

Amyotrophic lateral sclerosis (ALS) is caused by motor neuron death. The relationship between the prognosis of ALS patients and the function of their bone marrow mesenchymal stromal cells (BM-MSCs) is unclear. We designed this study to assess the correlation between the progression rate of the ALS Functional Rating Scale-revised version (δFS), which is reported to predict prognosis, and the pluripotency and trophic factor secreting capacity of ALS patients' BM-MSCs. We evaluated δFS in 23 ALS patients and isolated BM-MSCs from those patients and five healthy people. Levels of Nanog, Oct-4, and Nestin mRNA were examined to evaluate pluripotency, and levels of BDNF, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF-1α, GDNF, VEGF, and ANG mRNA were examined to assess trophic factor secreting capacity. In addition, we measured the protein levels of Nanog, Oct-4, Nestin, SDF-1α, ANG, bFGF-2, VEGF, IGF-1, GDNF, and BDNF. mRNA levels of Nanog, Oct-4, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF-1α, GDNF, VEGF, and ANG were negatively correlations with δFS. However, those of Nestin and BDNF were not significantly correlated with δFS. Similarly, Nanog, Oct-4, SDF-1α, ANG, bFGF-2, VEGF, IGF-1, and GDNF protein levels had a significant negative correlation with δFS. Results indicate that the pluripotency and trophic factor secreting capacity of the BM-MSCs of ALS patients are reduced in proportion to a poorer prognosis. We therefore suggest that healthy allogeneic BM-MSCs might be a better option for cell therapy in ALS patients. © 2011 Elsevier Inc..


Cho G.-W.,Chosun University | Kang B.Y.,Hanyang University | Kim K.-S.,CoreStem Inc. | Kim S.H.,Hanyang University
Neuroscience Letters | Year: 2012

The potential of human bone marrow-mesenchymal stromal cells (hBM-MSCs) to differentiate into diverse cell types and secrete a variety of trophic factors makes them an excellent cell therapy tool for intractable diseases. However, their therapeutic efficacy has not yet been satisfied in preclinical and/or clinical trials with autologous or allogenic stem cells. To improve the efficacy of stem cell therapy, optimized conditions for stem cells need to be defined. In this study, we evaluated the effects of valproic acid (VPA), an HDAC inhibitor, in human BM-MSCs and assessed the expression of trophic factors (ANG, BDNF, ECGF1, bFGF-2, GDNF, HGF, IGF-1, PIGF, TGF-β1, and β- Pix) in MSCs treated with 200. μg/ml VPA for 12. h. Under these conditions the features of MSCs were not changed. The VPA-treated MSCs also showed an increased cell protective effect against oxidative injuries in MTT assays and improved migratory ability when examined by the Boyden chamber assay. This suggests that MSCs may be improved by treatment with an optimal VPA dose and incubation time, which may increase the efficacy of stem cell therapy. © 2012 Elsevier Ireland Ltd.


Kwon M.-S.,Korea University | Noh M.-Y.,Hanyang University | Oh K.-W.,Hanyang University | Cho K.-A.,Hanyang University | And 4 more authors.
Journal of Neurochemistry | Year: 2014

In a previous study, we reported that intrathecal injection of mesenchymal stem cells (MSCs) slowed disease progression in G93A mutant superoxide dismutase1 transgenic mice. In this study, we found that intrathecal MSC administration vastly increased the infiltration of peripheral immune cells into the spinal cord of Amyotrophic lateral sclerosis (ALS) mice (G93A mutant superoxide dismutase1 transgenic). Thus, we investigated the immunomodulatory effect of MSCs on peripheral blood mononuclear cells (PBMCs) in ALS patients, focusing on regulatory T lymphocytes (Treg; CD4+/CD25high/FoxP3+) and the mRNA expression of several cytokines (IFN-c, TNF-a, IL-17, IL-4, IL-10, IL-13, and TGF-b). Peripheral blood samples were obtained from nine healthy controls (HC) and sixteen patients who were diagnosed with definite or probable ALS. Isolated PBMCs from the blood samples of all subjects were co-cultured with MSCs for 24 or 72 h. Based on a fluorescence- activated cell sorting analysis, we found that co-culture with MSCs increased the Treg/total T-lymphocyte ratio in the PBMCs from both groups according to the co-culture duration. Co-culture of PBMCs with MSCs for 24 h led to elevated mRNA levels of IFN-c and IL-10 in the PBMCs from both groups. However, after co-culturing for 72 h, although the IFNc mRNA level had returned to the basal level in co-cultured HC PBMCs, the IFN-c mRNA level in co-cultured ALS PBMCs remained elevated. Additionally, the levels of IL-4 and TGF-b were markedly elevated, along with Gata3 mRNA, a Th2 transcription factor mRNA, in both HC and ALS PBMCs cocultured for 72 h. The elevated expression of these cytokines in the co-culture supernatant was confirmed via ELISA. Furthermore, we found that the increased mRNA level of indoleamine 2,3-dioxygenase (IDO) in the co-cultured MSCs was correlated with the increase in Treg induction. These findings of Treg induction and increased anti-inflammatory cytokine expression in co-cultured ALS PBMCs provide indirect evidence that MSCs may play a role in the immunomodulation of inflammatory responses when MSC therapy is targeted to ALS patients. © 2014 International Society for Neurochemistry.


Kim H.Y.,Hanyang University | Kim H.,Laboratory Animal Center | Oh K.-W.,Hanyang University | Oh S.-I.,Hanyang University | And 5 more authors.
Stem Cells | Year: 2014

Bone marrow mesenchymal stromal cells (MSCs) can modify disease progression in amyotrophic lateral sclerosis (ALS) model. However, there are currently no accurate biological markers for predicting the efficacy of autologous MSC transplants in ALS patients. This open-label, singlearm, investigator-initiated clinical study was designed to identify markers of MSCs that could be used as potential predictors of response to autologous MSC therapy in patients with ALS. We enrolled 37 patients with ALS who received autologous MSCs via intrathecal injection in two monthly doses. After a 6-month follow-up period, the patients were categorized as responders and non-responders based on their scores on the revised ALS Functional Rating Scale (ALSFRSR). Biological markers including β-fibroblast growth factor-2, stromal cell-derived factor-1α, vascular endothelial growth factor (VEGF), insulin-like growth factor-1, brain-derived neurotrophic factor, angiogenin (ANG), interleukin (IL)24, IL-10, and transforming growth factor-β (TGF-β) were measured in the MSC cultures and their levels were compared between the responders and nonresponders. To confirm the markers' predictive ability, MSCs isolated from one patient in each group were transplanted into the cisterna magna of mutant SOD1G93A transgenic mice to measure their lifespans, locomotor activity, and motor neuron numbers. The levels of VEGF, ANG, and TGF-β were significantly higher in responders than in nonresponders. In the mouse model, the recipients of responder MSCs had a significantly slower onset of symptoms and a significantly longer lifespan than the recipients of nonresponders or controls. Our data suggest that VEGF, ANG, and TGF-β levels in MSCs could be used as potential biological markers to predict the effectiveness of autologous MSC therapy and to identify those patients who could optimally benefit from MSC treatment. © 2014 AlphaMed Press.


Patent
CoreStem Inc. | Date: 2015-05-01

The present invention relates to a cell culture flask for culturing a cell using a culture solution, particularly to a cell culture flask enabling to culture a cell without any contamination, to automatically introduce and discharge the culture solution or gases and to be stacked in turn, and a cell culture device having the same. The present invention provides a cell culture flask comprising a culture space with a predetermined area for culturing the cell; one or more culture solution inlet ports for introducing the culture solution or the cell into the culture space; one or more culture solution outlet ports for discharging the culture solution or the cell supplied to the culture space; and one or more gas inlet ports for introducing the various gases into the culture space, wherein the cell culture flask is made airtight and formed of a transparent material so that a user can see an internal portion of the cell culture flask, and a cell culture device having the same.


Patent
CoreStem Inc. | Date: 2010-10-19

The present invention relates to a composition for improving the migration potential of a stem cell, a method for evaluating the migration potential of a stem cell and a method for screening an adjuvant of cell therapy improving the migration potential of a stem cell. The present invention may be effectively used for enhancing the efficacy of neurological disease-treatment by inducing therapeutic stem cells to migrate efficiently to the lesion site.


Disclosed is a pharmaceutical composition for treating bone disease or countering inflammation containing cartilage stem cells as an active ingredient. The present disclosure provides a novel cell treatment regimen for bone disease and inflammatory disease using the cartilage stem cells as an active ingredient. When the cartilage stem cells of the present disclosure are administered into the articular capsule, the administered cartilage stem cells are highly effective in treating bone disease and inflammatory bone disease since they grow or differentiate into chondrocytes and exhibit an anti-inflammatory activity. Since the cartilage stem cells of the present disclosure do not express histocompatibility antigens which give rise to rejection in tissue or organ transplants, autologous cells or exogenous cells can be used during cell transplantation for treatment of bone disease and inflammation.


Disclosed is a cell culture tube, having in opposite end walls two respective eccentric openings which communicate with each other through an inner straight passage formed in the cell culture tube, in which the inner straight passage is tilted at an angle relative to a longitudinal axis of the cell culture tube to allow a culture medium to smoothly flow into and out of the inner passage through the openings. Also, provided is a multiple cell culture system using a plurality of the culture tubes.


Disclosed is a pharmaceutical composition for treating bone disease or countering inflammation containing cartilage stem cells as an active ingredient. The present disclosure provides a novel cell treatment regimen for bone disease and inflammatory disease using the cartilage stem cells as an active ingredient. When the cartilage stem cells of the present disclosure are administered into the articular capsule, the administered cartilage stem cells are highly effective in treating bone disease and inflammatory bone disease since they grow or differentiate into chondrocytes and exhibit an anti-inflammatory activity. Since the cartilage stem cells of the present disclosure do not express histocompatibility antigens which give rise to rejection in tissue or organ transplants, autologous cells or exogenous cells can be used during cell transplantation for treatment of bone disease and inflammation.

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