• Biotechnology and Bioprocess Engineering:BBE
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• 제9권1호
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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.

• Reproductive and Developmental Biology
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• 제31권4호
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• pp.241-248
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• 2007

Epigenetic modification dependent DNA methyltransferases (DNMTs) play an important role in tissue- and stage-specific gene regulation and normal mammalian development. In this study, we show that DNMTs are expressed at different levels during hematopoietic stem cell (HSC) differentiation to proerythrocytes. DNMT1, DNMT3A, and DNMT3B were highly expressed at day 7 after differentiation. We used specific siRNA as a tool to probe the relationship between the expression of DNMTs and erythropoietic differentiation. When introduced siRNA of DMNT1 and DMNT3b in human $CD34^+$ cells, these more differentiated into erythrocytes. This was confirmed by glycophorin A (GPA) positive cell analysis and globin gene expression. $GPA^+$ cells increased up to $20{\sim}30%$, and ${\gamma}$- and ${\epsilon}$-globin genes increased in siRNA transfected cells. Therefore, our data suggest that suppression of DNA methylation can affect positively differentiation of HSC and may contribute to expression of erythrocyte lineage genes including GPA and globins.

• IMMUNE NETWORK
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• 제15권3호
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• pp.125-134
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• 2015

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of $CD11b^+Gr-1^+$ myeloidderived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.

• 대한한의학회지
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• 제37권4호
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• pp.36-44
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• 2016

Objectives: Granulocyte-colony-stimulating factor (G-CSF) mobilized bone marrow (BM)-derived hematopoietic stem cells could contribute to improvement of liver function. In addition, liver fibrosis can reportedly be prevented by the Rg 1 component of red ginseng. This study investigated the combined effect of G-CSF and red ginseng on decompensated liver cirrhosis. Methods: Four patients with decompensated liver cirrhosis were injected with G-CSF to proliferate BM stem cells for 4 days ($5{\mu}g/kg$ bid subcutaneously) and followed-up for 3 months. The patients also received red ginseng for 4 days (2 tablets tid per os). We analyzed Child-Pugh scores, Model for End-Stage Liver Disease (MELD) scores and cirrhotic complications. Results: All patients showed marked increases in White blood cell (WBC) and CD34+ cells in the peripheral blood, with a peak time of 4 days after G-CSF injection. Spleen size also increased after G-CSF injection, but not severely. At end of the study, 2 patients showed improvement in Child-Pugh scores, hepatic encephalopathy, and refractory ascites. During the clinical trial period, none of the 4 patients showed any other adverse events or deterioration of liver function. Conclusions: We conclude that G-CSF/red ginseng combination therapy is relatively effective in improving liver function and major complications of decompensated liver cirrhosis without adverse effects. Further clinical trials are warranted to assess the clinical effects of G-CSF for decompensated liver cirrhosis.

• 한국막학회:학술대회논문집
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• 한국막학회 2004년도 Proceedings of the second conference of aseanian membrane society
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• pp.55-58
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• 2004

Cell separation from peripheral blood was investigated using surface-modified polyurethane (PU) membranes with different functional groups. Both red blood cells and platelets could pass through unmodified PU and PU-SO$_3$H membranes, while the red blood cells preferentially passed through PU-N(C$_2$H$_{5}$ )$_2$ and PU-NHC$_2$H$_4$OH membranes. The permeation ratio of T and B cells was less than 25% for the surface-modified and unmodified PU membranes. CD34$^{+}$ cells have been recognized as various kinds of stem cells including hematopoietic and mesenchymal stem cells. The adhesiveness of CD34$^{+}$ cells on the PU membranes was found to be higher than that of red blood cells, platelets, T cells or B cells. Overall, the adhesiveness of blood cells on the PU membranes increased in the following order: red blood cells $\leq$ platelets ＜ T cells $\leq$ B cells ＜ CD34$^{+}$ cells. Treatment of PU-COOH membranes with a human albumin solution to detach adhered blood cells, allowed recovery of mainly CD34$^{+}$ cells in the permeate, while both red blood cells and platelets could be isolated in the permeate using unmodified PU membranes. The PU membranes showed different permeation and recovery ratios of specific cells depending on the functional groups attached to the membranes.mbranes.

• 한국한의학연구원논문집
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• 제10권1호
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• pp.127-135
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• 2004

Hematopoietic stem cells in bone marrow form all kinds of blood cells. In traditional medicine, functions of bone marrow cells are very similar to those of Essence(精) which is a fundamental factor of physical development and reproduction. Our experiment examined the effect of deer blood on aplastic anemia induced mouse using cyclophosphamide 150 mg/kg i.p injection before experiment and then another cyclophosphamide 120 mg/kg i.p injection on day 10. Then we administrated dried deer blood in distilled water for 5 days, 9 days and 10 days. We examined blood and marrow samples. In results, deer blood showed a trend of effectiveness on recovery of red blood cells and erythropoietin although they were not statistical significant. And deer blood did not show changes in CD34.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.77-77
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• 2003

Coculture of HSC with bone marrow-derived mesenchymal stem cells (BM-MSCs) is one of used methods to increase cell numbers before transplant to the patients. However, because of difficulties to purify HSCs after coculture with BM-MSCs, it needs to develop a method to overcome the problem. In the present study, we have examined whether a culture insert placed over a feeder layer might support the expansion of HSCs within the insert. $CD34^+/ $ cells isolated from the umbilical cord blood by using midiMACS were divided into three groups. A group of 1 $\times$ $10^5$ cells were grown on a culture insert without feeder layer (Direct). The same number of HSCs was directly cocultured with BM-MSCs (Contact). The third group was placed onto an insert below which BM-MSCs were grown (Insert). To distinguish feeder cells from HSCs, BM-MSCs was pre-labeled fluorescently with PKH26 and 1 $\times$ $10^5$ cells were seeded in the culture dishes. After culture for 13 days, the expansion factor (x) of HSCs that were grown without feeder layer (Direct) was $26.6 \pm 8.4.$ In contrast, the number of HSCs directly cocultured with feeder layer was 59.6 $\pm$ 0.5 and that of HSCs cultured onto an insert was $46.9 \pm 8.4.$ The percentage of BM-MSCs cells remained being fluorescent was $97.9 \pm 0.3%$ after culture. Immune-phenotypically large proportion of cultured cells were founded to be differentiated into myeloid/monocyte progenitor cells. The ability of BM-MSCs, fetal lung, cartilage and brain tissue cells to support ex vivo expansion of HSCs was also examined using the insert. After 11 days of coculture with each of these cells, the expansion factor of HSCs was 15.0, 39.0, 32.0 and 24.0, respectively. Based upon these observations, it is concluded that the coculture method using insert is very effective to support ex vivo expansion of HSCs and to eliminate the contamination of other cells used to coculture wth HSCs.

• 대한치과교정학회지
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• 제42권5호
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• pp.249-254
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• 2012

Objective: To investigate the stem cell-like characteristics of human periodontal ligament (PDL) stromal cells outgrown from orthodontically extracted premolars and to evaluate the potential for myogenic differentiation. Methods: PDL stromal cells were obtained from extracted premolars by using the outgrowth method. Cell morphological features, self-replication capability, and the presence of cell-surface markers, along with osteogenic, adipogenic, and chondrogenic differentiation, were confirmed. In addition, myogenic differentiation was induced by the use of 5-aza-2'-deoxycytidine (5-Aza) for DNA demethylation. Results: PDL stromal cells showed growth patterns and morphological features similar to those of fibroblasts. In contrast, the proliferation rates of premolar PDL stromal cells were similar to those of bone marrow and adipogenic stem cells. PDL stromal cells expressed surface markers of human mesenchymal stem cells (i.e., CD90 and CD105), but not those of hematopoietic stem cells (i.e., CD31 and CD34). PDL stromal cells were differentiated into osteogenic, adipogenic, and chondrogenic lineages. Myotube structures were induced in PDL stromal cells after 5-Aza pretreatment, but not in the absence of 5-Aza pretreatment. Conclusions: PDL stromal cells isolated from extracted premolars can potentially be a good source of postnatal stem cells for oromaxillofacial regeneration in bone and muscle.

• Journal of Yeungnam Medical Science
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• 제36권2호
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• pp.148-151
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• 2019

The dose of CD34+ cells is known to influence the outcome of allogeneic peripheral blood stem cell (PBSC) and/or T-cell-depleted transplantation. A previous study proposed that $2{\times}10^6\;CD34+\;cells/kg$ is the ideal minimum dose for allogeneic transplantation, although lower doses did not preclude successful therapy. In the case we present here, CD34+ cells were collected from a matched sibling donor on the day of allogeneic hematopoietic stem cell transplantation; however, the number of cells was not sufficient for transplantation. Consequently, PBSCs were collected three additional times and were infused along with cord blood cells from the donor that were cryopreserved at birth. The cumulative dose of total nuclear cells and CD34+ cells was $15.9{\times}10^8\;cells/kg$ and $0.95{\times}10^6\;cells/kg$, respectively. White blood cells from this patient were engrafted on day 12. In summary, we report successful engraftment after infusion of multiple low doses of CD34+ cells in a patient with severe aplastic anemia.

• Journal of Microbiology and Biotechnology
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• 제32권12호
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• pp.1615-1621
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• 2022

Tissue regeneration is the ultimate treatment for many degenerative diseases, however, repair and regeneration of damaged organs or tissues remains a challenge. Previously, we showed that B1 Ab and H3 Ab induce stem cells to differentiate into microglia and brown adipocyte-like cells, while trafficking to the brain and heart, respectively. Here, we present data showing that another selected agonist antibody, P1 antibody, induces the migration of cells to the pancreatic islets and differentiates human stem cells into beta-like cells. Interestingly, our results suggest the purified P1 Ab induces beta-like cells from fresh, human CD34⁺ hematopoietic stem cells and mouse bone marrow. In addition, stem cells with P1 Ab bound to expressed periostin (POSTN), an extracellular matrix protein that regulates tissue remodeling, selectively migrate to mouse pancreatic islets. Thus, these results confirm that our in vivo selection system can be used to identify antibodies from our library which are capable of inducing stem cell differentiation and cell migration to select tissues for the purpose of regenerating and remodeling damaged organ systems.