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PubMed | National Institute of Allergy and Infectious Diseases, CoreStem Inc., Hanyang University and Chungbuk National University
Type: | Journal: Scientific reports | Year: 2017

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Fas


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 Y.S.,Hanyang University | Noh M.Y.,Hanyang University | Cho K.A.,Hanyang University | Kim H.,Hanyang University | And 5 more authors.
Molecular Neurobiology | Year: 2015

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent a promising tool for stem cell-based therapies. However, the majority of MSCs fail to reach the injury site and have only minimal therapeutic effect. In this study, we assessed whether hypoxia/reoxygenation (H/R) preconditioning of human BM-MSCs could increase their functional capacity and beneficial effect on ischemic rat cortical neurons. Human BM-MSCs were cultured under hypoxia (1 % O2) and with long-term reoxygenation for various times to identify the optimal conditions for increasing their viability and proliferation. The effects of H/R preconditioning on the BM-MSCs were assessed by analyzing the expression of prosurvival genes, trophic factors, and cell migration assays. The functionally improved BM-MSCs were cocultured with ischemic rat cortical neurons to compare with normoxic cultured BM-MSCs. Although the cell viability and proliferation of BM-MSCs were reduced after 1 day of hypoxic culture (1 % O2), when this was followed by 5-day reoxygenation, the BM-MSCs recovered and multiplied extensively. The immunophenotype and trilineage differentiation of BM-MSCs were also maintained under this H/R preconditioning. In addition, the preconditioning enhanced the expression of prosurvival genes, the messenger RNA (mRNA) levels of various trophic factors and migration capacity. Finally, coculture with the H/R-preconditioned BM-MSCs promoted the survival of ischemic rat cortical neurons. H/R preconditioning of BM-MSCs increases prosurvival signals, trophic factor release, and cell migration and appears to increase their ability to rescue ischemic cortical neurons. This optimized H/R preconditioning procedure could provide the basis for a new strategy for stem cell therapy in ischemic stroke patients. © 2014, Springer Science+Business Media New York.


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.


Cho G.-W.,Hanyang University | Noh M.-Y.,Hanyang University | Kim H.Y.,Hanyang University | Koh S.-H.,Hanyang University | And 2 more authors.
Stem Cells and Development | Year: 2010

Human bone marrow stromal cells (BM-SCs) possess the potential to differentiate, self-renew, and produce diverse trophic/growth factors and are an excellent cell therapy tool for degenerative diseases. However, they exhibit different therapeutic efficacies, depending on the health status and age of the cell donor. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron death in the central nervous system. In this study, we isolated BM-SCs from 11 ALS patients and characterized their potential secretory capacity of neurotrophic factors. We identified significant reductions in the expression of Oct-4 and Nanog, and in the trophic factors ANG, FGF-2, HGF, IGF-1, PIGF, SDF-1α, TGF-β, and VEGF, but not in BDNF or ECGF. Migration of ALS-SCs was reduced, although the cells expressed the same markers for human mesenchymal phenotypes. These data suggest that ALS-SCs have diminished capacity as trophic mediators and may have reduced beneficial effects in cell therapy. © 2010 Mary Ann Liebert, Inc.


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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