• Journal of Life Science
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• v.32 no.6
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• pp.468-475
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• 2022

The functional distinction between stem and progenitor cells is well established in several tissues, particularly in the blood. There, hematopoietic stem cells preserve their self-renewal potential and reconstitution ability in the bone marrow niche. Bone marrow represents a unique setting in which to examine how stroma influences tissue function. It was the setting in which the experimental definition of a niche was first provided in mammalian stem cell biology and where clear evidence for non-cell-autonomous oncogenesis was first defined. The relationship between bone and blood is ancient as all animals since the divergence of fish that have bones and blood, make blood in their bones. This long coevolution engendered complex interrelationships, including the first proposed and first experimentally defined niche for stem cells in mammals. Multiple bone marrow stromal cell types serve as regulators of hematopoiesis, and the dysfunction of some causes myelodysplasia and leukemia. However, no comprehensive atlas of stromal subpopulations exists. Therefore, we think these data point to something of importance, such as how the needs and challenges of the organism become translated down to distinct cell types that critically govern specific functions within tissues and do so at the level of a single molecule. We think this will be of broad interest to those focusing on systems biology and the physiology of organisms, particularly those seeking a molecular basis for understanding cell and tissue behavior. We summarized the current and emerging concepts of hematopoietic stem cells and bone marrow niche.

• 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.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.775-778
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• 2001

Chemokines are small chemotalic cytokines that have a number of biological functions. Some chemokines regulate the proliferation of hematopoietic stem and progenitor cells(HSPC). Leukotactin-l(Lkn-l) is a CC chemokine and is known to reduce colony forming unit(CFU). The N-terminal truncated Leukotactin-l(rtLkn-l), produced by Pichia pastoris, suppressed CFU from 40 to 60%. The rtLkn-l protected CFU from cytotoxic effect of anticancer drug such as Ara-C, doxorubicin, cyclophosphamide and 5-FU by cell cycle arrest.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.166-174
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• 2002

Background: Human umbilical cord bloods, which could be taken during the delivery are utilized as a source of hematopoietic stem cells. Also in cord blood, there are several kinds of stem cells such as endothelial and mesenchymal stem cells. Methods: We isolated the mesenchymal stem cells from human umbilical cord bloods and confirmed the differentiation of these cells into osteoblast progenitor cells. The mesenchymal stem cells derived from umbilical cord blood have the ability to differentiate into specific tissue cells, which is one of characteristics of stem cells. These cells were originated from the multipolar shaped cells out of adherent cells of the umbilical cord blood mononuclear cell culture. Results: The mesenchymal stem cells expressed cell surface antigen CD13, CD90, CD102, CD105, ${\alpha}$-smooth muscle actin and cytoplasmic antigen vimentine. Having cultrued these cells in bone formation media, we observed the formation of extracellular matrix and the expression of alkaline phosphatase and of mRNA of cbfa-1, ostoecalcin and type I collagen. Conclusion: From these results we concluded that the cells isolated from the umbilical cord blood were mesenchymal stem cells, which we could differentiate into osteoblast when cultured in bone formation media. In short, it is suggested that these cells could be used as a new source of stem cells, which has the probability to alternate the embryonic stem cells.

• BMB Reports
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• v.56 no.9
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

• Reproductive and Developmental Biology
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• v.32 no.1
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• pp.1-7
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• 2008

The SCID-repopulation cells(SRCs) assay has been widely used to determine the self-renewal capacity of hematopoietic stem cells (HSCs). In this study, we tested the repopulating efficiency of porcine bone marrow derived hematopoietic stem cells using nonobese diabetic/severe combined immunodieficient (NOD/SCID) mice which was inherited immunodeficiency mire with defect of T cells, B cells, and low activity of NK cells. We transplanted porcine bone marrow hematopoietic stem/progenitor cells with intraperitoneal injection into neonate NOD/SCID mice. We confirmed efficient reconstitution activity of inoculated porcine hematopoietis cells in variety of organs of NOD/SCID mice. Interestingly, pig $CD3^+$ T lymphocytes detected with high level in liver($15.6{\pm}3.7%$), spleen($5.6{\pm}3.0%$), thymus($1.5{\pm}1.3%$), and BM($2.3{\pm}0.9%$), respectively. These data imply that microenvironment of neonate NOD/SCID mice is very efficient for proliferation and differentiation of porcine T cells, and can be useful for the study of T cells development and renogeneic organ transplantation.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.7-11
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• 2004

Leukotactin-1 (Lkn-1), a human CC chemokine, has been demonstrated to induce chemotaxis of neutrophils, monocytes, eosinophils and Iym phocytes and has been shown to suppress colony formation of hematopoietic stem and progenitor cells (HSPC) in vitro and in vivo. The temporal suppression of HSPC by chemokines could potentially be applicable for various indications, such as the protection of HSPC from the several anti-proliferating chemotherapeutics in cancer treatments. In order to evaluate the protective effects on myeloid progenitor cells, the recombinant Lkn-1 was produced by Pichia pastoris and tested with cyclophosphamide, cytotoxic chemotherapeutics. The pretreatment of Lkn-1 increased the number of HSPC in bone marrow as well as the potency of resulting progenitor cells after the treatment of cyclophosphamide. Af-ter the first cycle of cyclophosphamide treatment these protections of HSPC correlated with the increased number of white blood cells and neutrophils in the peripheral blood. In lethal conditions created by the repeated administration of cyclophosphamide, the treatment of Lkn-1 enhanced the survival of mice, suggesting the potential use of Lkn-1 as the protective agent for HSPC from various cytotoxic insults.

• Development and Reproduction
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• v.9 no.2
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• pp.105-114
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• 2005

Embryonic stem(ES) cells have tremendous potential as a cell source for cell-based therapies. Realization of that potential will depend on our ability to understand and manipulate the factors that influence cell fate decision and to develop methods for getting enough cell numbers for clinical applications. Hematopoiesis has been widely studied, and hematopoietic differentiation from ES cells is a good model to study lineage commitment. In this study, we investigated stemness and compared the efficiency of hematopoietic differentiation using two different mouse embryonic stem cell lines TC-1 and B6-1. Although the two cell lines showed known stem cell properties with minor differences, the embryoid body formation efficiency in methylcellulose was much higher in TC-1 than B6-1. When measured potentials of hematopoietic differentiation using functional(colony-forming cell) and phenotypic(specific marker expression) assays, we found that TC-1 can differentiate into hematopoietic cells in methylcellulose culture but B6-1 cannot. These results imply that we can improve the efficiency of hematopoietic cell differentiation by selection of proper cell lines and this may be also applied in the differentiation of human embryonic stem cells.

• Molecules and Cells
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• v.24 no.3
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• pp.343-350
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• 2007

Mesenchymal stem/progenitor cells (MPCs) were isolated from porcine umbilical cord blood (UCB) and their morphology, proliferation, cell cycle status, cell-surface antigen profile and expression of hematopoietic cytokines were characterized. Their capacity to differentiate in vitro into osteocytes, adipocytes and chondrocytes was also evaluated. Primary cultures of adherent porcine MPCs (pMPCs) exhibited a typical fibroblast-like morphology with significant renewal capacity and proliferative ability. Subsequent robust cell growth was indicated by the high percentage of quiescent (G0/G1) cells. The cells expressed the mesenchymal surface markers, CD29, CD49b and CD105, but not the hematopoietic markers, CD45 and CD133 and synthesized hematopoietic cytokines. Over 21 days of induction, the cells differentiated into osteocytes adipocytes and chondrocytes. The expression of lineage specific genes was gradually upregulated during osteogenesis, adipogenesis and chondrogenesis. We conclude that porcine umbilical cord blood contains a population of MPCs capable of self-renewal and of differentiating in vitro into three classical mesenchymal lineages.

• Journal of Life Science
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• v.31 no.9
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• pp.856-861
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• 2021

CD82/KAI1, identified as a metastasis suppressor, was initially known only as a molecular facilitator, but its various functions have recently been revealed. CD82 plays an important role in the stem-progenitor cell, angiogenesis, and muscle. We would like to introduce the recently reported functions and roles of CD82 in this review. CD82 is a member of the tetraspanin family, which consists of four transmembrane domains. The interaction between CD82 and cell adhesion molecules suppresses the metastasis of cancer. CD82 regulates the cell cycle of stem-progenitor cells in the stem cell niche. In the bone marrow, CD82 is expressed on long-term repopulating hematopoietic stem cells (LT-HSCs), which show multipotent differentiation potential. The interaction between CD82 and Duffy antigen receptor for chemokines (DARC) induces quiescence in LT-HSCs. CD82 also regulates Rac1 activity, resulting in the homing and engraftment of HSCs into the bone marrow niche. Besides, CD82 maintains the differentiation potential of muscle stem cells and prevents angiogenesis by inhibiting the expression of cytokines, such as IL-6 and VEGF and adhesion molecules in endothelial cells. CD82 is a key membrane protein that distinguishes the hierarchy of stem-progenitor cells, and is also important for amplification and verification of cellular resources. Further studies on the function of CD82 in various organs and cells are expected to advance cell biology and cell therapy.