• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.1.1-1.10
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• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• Clinical and Experimental Reproductive Medicine
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• v.46 no.1
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• pp.1-7
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• 2019

With the progress of regenerative medicine, mesenchymal stem cells (MSCs) have received attention as a way to restore ovarian function. It has been reported that MSCs derived from bone marrow, adipose, umbilical cord blood, menstrual blood, and amniotic fluid improved ovarian function. In light of previous studies and advances in this field, there are increased expectations regarding the utilization of MSCs to restore ovarian function. This review summarizes recent research into potential applications of MSCs in women with infertility or primary ovarian insufficiency, including cases where these conditions are induced by anticancer therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.1
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• pp.65-68
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• 2001

The major manifestations of aplastic anemia are characterized by persistent bone marrow aplasia and peripheral pancytopenia due to defective stem cells in which differentiation is not curtailed or preferential elimination of stem cells with self-renewal capacity, which results in serious complications such as bleeding and infection. Recent advances in the therapeutic modalities, such as bone marrow transplantation and immunosuppressive therapy, and in supportive measures as component transfusion and infection control with better quality of antibiotics resulted in an improved survival and subsequently increased possibility of complications which need surgical intervention. Considering the fact that surgery may not only control complications, but offers the opportunity to give effective therapy for aplastic anemia and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed. We report a case of patient with aplastic anemia who had been performed surgical intervention of partial maxillectomy for the squamous cell carcinoma on maxilla without serious complications during perioperative and postoperative period.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.54-65
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• 2014

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, with the ability to differentiate into different cell types. Additionally, the immunomodulatory activity of MSCs can downregulate inflammatory responses. The use of MSCs to repair injured tissues and treat inflammation, including in neuroimmune diseases, has been extensively explored. Although MSCs have emerged as a promising resource for the treatment of neuroimmune diseases, attempts to define the molecular properties of MSCs have been limited by the heterogeneity of MSC populations. We recently developed a new method, the subfractionation culturing method, to isolate homogeneous human clonal MSCs (hcMSCs). The hcMSCs were able to differentiate into fat, cartilage, bone, neuroglia, and liver cell types. In this study, to better understand the properties of neurally differentiated MSCs, gene expression in highly homogeneous hcMSCs was analyzed. Neural differentiation of hcMSCs was induced for 14 days. Thereafter, RNA and genomic DNA was isolated and subjected to microarray analysis and DNA methylation array analysis, respectively. We correlated the transcriptome of hcMSCs during neural differentiation with the DNA methylation status. Here, we describe and discuss the gene expression profile of neurally differentiated hcMSCs. These findings will expand our understanding of the molecular properties of MSCs and contribute to the development of cell therapy for neuroimmune diseases.

• Molecules and Cells
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• v.24 no.1
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

• Journal of Microbiology and Biotechnology
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• v.32 no.1
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• pp.126-140
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• 2022

Stem cells can be applied usefully in basic research and clinical field due to their differentiation and self-renewal capacity. The aim of this study was to establish an effective novel therapeutic cellular source and create its molecular expression profile map to elucidate the possible therapeutic mechanism and signaling pathway. We successfully obtained a mesenchymal stem cell population from human embryonic stem cells (hESCs) cultured on chemically defined feeder-free conditions and treated with connective tissue growth factor (CTGF) and performed the expressive proteomic approach to elucidate the molecular basis. We further selected 12 differentially expressed proteins in CTGF-induced hESC-derived mesenchymal stem cells (C-hESC-MSCs), which were found to be involved in the metabolic process, immune response, cell signaling, and cell proliferation, as compared to bone marrow derived-MSCs(BM-MSCs). Moreover, these up-regulated proteins were potentially related to the Wnt/β-catenin pathway. These results suggest that C-hESC-MSCs are a highly proliferative cell population, which can interact with the Wnt/β-catenin signaling pathway; thus, due to the upregulated cell survival ability or downregulated apoptosis effects of C-hESC-MSCs, these can be used as an unlimited cellular source in the cell therapy field for a higher therapeutic potential. Overall, the study provided valuable insights into the molecular functioning of hESC derivatives as a valuable cellular source.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7415-7423
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• 2015

Chronic myeloid leukemia (CML) is a stem cell disorder characterized by unrestricted proliferation of the myeloid series that occurs due to the BCR-ABL fusion oncogene as a result of reciprocal translocation t(9;22) (q34;q11). This discovery has made this particular domain a target for future efforts to cure CML. Imatinib revolutionized the treatment options for CML and gave encouraging results both in case of safety as well as tolerability profile as compared to agents such as hydroxyurea or busulfan given before Imatinib. However, about 2-4% of patients show resistance and mutations have been found to be one of the reasons for its development. European Leukemianet gives recommendations for BCR-ABL mutational analysis along with other tyrosine kinase inhibitors (TKIs) that should be administered according to the mutations harbored in a patient. The following overview gives recommendations for monitoring patients on the basis of their mutational status.

• Journal of Periodontal and Implant Science
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• v.35 no.4
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• pp.1097-1108
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• 2005

The present study was to determine the influence of micro-macro biphasic calcium phosphate(MBCP) on proliferation and differentiation of human marrow-derived mesenchymal stem cells. Primary stem cells were cultured from bone marrow and 3-4 passaged cells were used. This study tested the proliferative effects by cell counting. Collagen sythensis, alkaline phosphatase activity, expression of osteocalcin and bone sialoprotein by Western blot analysis were evaluated. The cellular proliferation of ASC was not influenced by MBCP. Collagen synthesis of ASC cultured on MBCP significantly increased at 5th and 7th days(p<0.05). The ALP activity in ASC cultured on MBCP significantly increased at 5th and 7th days(p<0.05). The expression of OC and BSP incresaed in ASC cultured on MBCP. These results suggest that MBCP may stimulates the osteoblastic activity of ASC.

• Journal of Embryo Transfer
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• v.32 no.2
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• pp.39-45
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• 2017

Mesenchymal stem cells (MSCs) have been considered an alternative source of neuronal lineage cells, which are difficult to isolate from brain and expand in vitro. Previous studies have reported that MSCs expressing Nestin ($Nestin^+$ MSCs), a neuronal stem/progenitor cell marker, exhibit increased transcriptional levels of neural development-related genes, indicating that $Nestin^+$ MSCs may exert potential with neurogenic differentiation. Accordingly, we investigated the effects of the presence of $Nestin^+$ MSCs in bone-marrow-derived primary cells (BMPCs) on enhanced neurogenic differentiation of BMPCs by identifying the presence of $Nestin^+$ MSCs in uncultured and cultured BMPCs. The percentage of $Nestin^+$ MSCs in BMPCs was measured per passage by double staining with Nestin and CD90, an MSC marker. The efficiency of neurogenic differentiation was compared among passages, revealing the highest and lowest yields of $Nestin^+$ MSCs. The presence of $Nestin^+$ MSCs was identified in BMPCs before in vitro culture, and the highest and lowest percentages of $Nestin^+$ MSCs in BMPCs was observed at the third (P3) and fifth passages (P5). Moreover, significantly the higher efficiency of differentiation into neurons, oligodendrocyte precursor cells and astrocytes was detected in BMPCs at P3, compared with P5. In conclusion, these results demonstrate that neurogenic differentiation can be enhanced by increasing the proportion of $Nestin^+$ MSCs in cultured BMPCs.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.6
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• pp.337-342
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• 2008

Human bone marrow mesenchymal stem cells (hBM-MSCs) represent a potentially valuable cell type for clinical therapeutic applications. The present study was designed to evaluate the effect of long-term culturing (up to $10^{th}$ passages) of hBM-MSCs from eight individual amyotrophic lateral sclerosis (ALS) patients, focusing on functional ion channels. All hBM-MSCs contain several MSCs markers with no significant differences, whereas the distribution of functional ion channels was shown to be different between cells. Four types of $K^+$ currents, including noise-like $Ca^{+2}$-activated $K^+$ current ($IK_{Ca}$), a transient outward $K^+$ current ($I_{to}$), a delayed rectifier $K^+$ current ($IK_{DR}$), and an inward-rectifier $K^+$ current ($K_{ir}$) were heterogeneously present in these cells, and a TTX-sensitive $Na^+$ current ($I_{Na,TTX}$) was also recorded. In the RT-PCR analysis, Kv1.1,, heag1, Kv4.2, Kir2.1, MaxiK, and hNE-Na were detected. In particular, ($I_{Na,TTX}$) showed a significant passage-dependent increase. This is the first report showing that functional ion channel profiling depend on the cellular passage of hBM-MSCs.