• 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.

• IMMUNE NETWORK
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• v.7 no.3
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• pp.149-157
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• 2007

Background: The microsatellites within human leukocyte antigen (HLA) region show considerable polymorphism and strong linkage disequilibrium (LD) with HLA alleles. These microsatellites have been used for genetic analysis including disease mapping to understand susceptibility to autoimmune and infectious diseases. Also, use of microsatellites has recently been proposed as an approach for identifying non-HLA markers within the HLA region that could function as transplantation determinants and for the selection of potential donors for transplantation. Methods: To analyse the frequency of five microsatellites in the Korean population, genotyping for polymorphisms at five microsatellites markers (BAT2, MIB, DQCAR, D6S105 and TNFd) within HLA region was performed on 143 healthy Korean controls. Results: The most frequent genotype shown in healthy Korean controls were BAT2 8 (153 bp, 42.7%), MIB 1 (326 bp, 40.6%), DQCAR 3 (188 bp, 38.5%), D6S105 7 (126 bp, 58.0%) and TNFd 3 (128 bp, 58.0%). And common two-loci haplotypes were found as MIB 1-HLA-B*62 (HF: 10.6%), MIB 6-HLA-B*44 (HF: 7.8%), DQCAR 3-HLA-DRB1*13 (HF: 8.5%), TNFd 5-HLA-B*62 (HF: 7.8%) and D6S105 7-HLA-A*02 (HF: 16.2%). Conclusion: These data might provide useful information on the microsatellites markers with HLA region in Korean population and be helpful in further defining the clinical impact of these microsatellites.

• Molecules and Cells
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• v.43 no.2
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• pp.126-138
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• 2020

The transcription factor RUNX1 first came to prominence due to its involvement in the t(8;21) translocation in acute myeloid leukemia (AML). Since this discovery, RUNX1 has been shown to play important roles not only in leukemia but also in the ontogeny of the normal hematopoietic system. Although it is currently still challenging to fully assess the different parameters regulating RUNX1 dosage, it has become clear that the dose of RUNX1 can greatly affect both leukemia and normal hematopoietic development. It is also becoming evident that varying levels of RUNX1 expression can be used as markers of tumor progression not only in the hematopoietic system, but also in non-hematopoietic cancers. Here, we provide an overview of the current knowledge of the effects of RUNX1 dosage in normal development of both hematopoietic and epithelial tissues and their associated cancers.

• Reproductive and Developmental Biology
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• v.32 no.1
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• pp.9-14
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• 2008

Efficient gene transfer into hematopoietic stem cells is a great tool for gene therapy of hematopoietic disease. Retrovirus have been extensively used for gene delivery and gene therapy. However, current in vitro gene transfer has some obstacles suck as induction of differentiation loss of self-renewal capacity, and down-regulation of homing efficiency for in vitro hematopoietic stem cells transplantation. To overcome these problems, we developed efficient in vitro retroviral transfer technique by direct intra-bone marrow injection (IBM). We identified effective retrovirus gene transfer in bone marrow hematopoietic cells in vitro. Two weeks after retrovirus transfer via IBM injection, we observed stable EGFP gene expression in bone marrow, lymph node, spleen, and liver cells. In addition, $6.4{\pm}2.7%$ of hematopoietic stem/progenitor cells were expressed EGFP transgene from flow cytometry analysis. Our results demonstrate that in vitro retrovirus gene transfer via IBM injection can provide a viable alternative to current or moo gene transfer approach.

• Molecules and Cells
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• v.21 no.3
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• pp.343-355
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• 2006

Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation, although a wide variety of adult stem cells as well as embryonic stem cells have been identified and stem cell plasticity has recently been reported. To identify genes implicated in the control of the stem cell state as well as the characteristics of each stem cell line, we analyzed the expression profiles of genes in human embryonic, hematopoietic ($CD34^+$ and $CD133^+$), and mesenchymal stem cells using cDNA microarrays, and identified genes that were differentially expressed in specific stem cell populations. In particular we were able to identify potential hESC signature-like genes that encode transcription factors (TFAP2C and MYCN), an RNA binding protein (IMP-3), and a functionally uncharacterized protein (MAGEA4). The overlapping sets of 22 up-regulated and 141 down-regulated genes identified in this study of three human stem cell types may also provide insight into the developmental mechanisms common to all human stem cells. Furthermore, our comprehensive analyses of gene expression profiles in various adult stem cells may help to identify the genetic pathways involved in self-renewal as well as in multi-lineage specific differentiation.

• BMB Reports
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• v.50 no.3
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• pp.138-143
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• 2017

Ovariectomy-induced bone loss is related to an increased deposition of osteoclasts on bone surfaces. We reported that the 36-amino-acid-long neuropeptide Y (NPY) could mobilize hematopoietic stem/progenitor cells (HSPCs) from the bone marrow to the peripheral blood by regulating HSPC maintenance factors and that mobilization of HSPCs ameliorated low bone density in an ovariectomy-induced osteoporosis mouse model by reducing the number of osteoclasts. Here, we demonstrated that new NPY peptides, recombined from the cleavage of the full-length NPY, showed better functionality for HSPC mobilization than the full-length peptide. These recombinant peptides mediated HSPC mobilization with greater efficiency by decreasing HSPC maintenance factors. Furthermore, treatment with these peptides reduced the number of osteoclasts and relieved ovariectomy-induced bone loss in mice more effectively than treatment with full-length NPY. Therefore, these results suggest that peptides recombined from full-length NPY can be used to treat osteoporosis.

• BMB Reports
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• v.48 no.12
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• pp.645-646
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• 2015

The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.179-186
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• 2001

Bone marrow stroma is a complex tissue encompassing a number of cell types and supports hematopiesis, differentiation of erythreid, nyel and lymphoid lineages, and also maintains undifferentiated hematopoietic stem cells. Marrow-derived stem cells were composed of two populations, namely, hematopoietic stem cells that can differentiate into blood elements and mesenchymal stem cells that can give rise to connective tissues such as bone, cartilage, muscle, tendon, adipose and stroma. Differentiation requires environmental factors and unique intracellular signaling. For example, $TGF-{\beta}$ or BMP2 induces osteoblastic differentiation of mesenchymal stem are very exciting. However, the intrinsic controls involved in differentiation of stem cells are yet to be understood properly in order to exploit the same. This review presents an overview of the recent developments made in mesenchymal stem cell research with respect to osteogenesis.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.24-29
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• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• Journal of Food Hygiene and Safety
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• v.24 no.1
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• pp.78-85
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• 2009

This study was performed to investigate the effect of extract mixture(IPGE) drink from Inonotus Obliquus, Phellinus Linteus and Ganoderma Lucidum on hematopoietic stem cells and lymphocyte subset[lymphocyte, $CD4^+T$ cell, $CD8^+T$ cell, Natural Killer(NK) cells] of blood in 37 participants who were healthy and about $40{\sim}70$ years old. They were divided into two groups; extract mixture drink administration group(n=27) and placebo administration group(n=12). They were given the test drink daily for 4 weeks. Blood was obtained from the subjects every two week in the beginning of administration day to evaluate the $CD34^+$ hematopoietic stem cells and immune cells. As results, $CD34^+$ hematopoietic stem cells were significantly increased after taking IPGE drink for 4 weeks compared to that before taking the drink (p<0.001). There was no significant changes in number of lymphocytes, $CD4^+T$ cells, $CD8^+T$ cells, NK cells and in the ratio of $CD4^+/CD8^+$ cell after taking the test drink. From these results, it was suggested that IPGE have a good health effect by promoting the proliferation of the hematopoietic stem cells.