• IMMUNE NETWORK
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• v.4 no.2
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• pp.88-93
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• 2004

Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.519-523
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• 2007

Aplastic anemia is a rare disease, which is characterized by pancytopenia and hypocellular bone marrow without infiltration of abnormal cells or fibrosis. The incidence in Asia is higher than in the West and new cases are diagnosed at a rate of 5.1 per million pediatric populations per year in Korea. The pathophysiology is understood roughly by defective hematopoiesis, impaired bone marrow micro-environment and immune mechanism. Treatments are performed on basis of pathogenesis and selected depending on the severity. Immunosuppressive therapy with antilymphocyte or antithymocyte globulin and cyclosporine is effective in the majority of patients but has some problems including relapse or clonal evolution. Recently, there have been clinical trials of immunosuppression with hematopoietic growth factors or other drugs. Allogeneic hematopoietic stem cell transplantation (HSCT) is curative in children with severe aplastic anemia. The overall survival in HSCT from HLA-identical sibling is higher than alternative donor, including HLA matched unrelated donor or cord blood. We have to consider quality of life after HSCT because of high survival rate. However, chronic graft versus host disease and graft failure are important factors that affect the quality of life and overall survival. We need further investigation to make new regimens aimed at overcoming these risk factors and perform clinical trials.

• Archives of Plastic Surgery
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• v.44 no.3
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• pp.188-193
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• 2017

Alveolar cleft is a tornado-shaped bone defect in the maxillary arch. The treatment goals for alveolar cleft are stabilization and provision of bone continuity to the maxillary arch, permitting support for tooth eruption, eliminating oronasal fistulas, providing an improved esthetic result, and improving speech. Treatment protocols vary in terms of the operative time, surgical techniques, and graft materials. Early approaches including boneless bone grafting (gingivoperiosteoplasty) and primary bone graft fell into disfavor because they impaired facial growth, and they remain controversial. Secondary bone graft (SBG) is not the most perfect method, but long-term follow-up has shown that the graft is absorbed to a lesser extent, does not impede facial growth, and supports other teeth. Accordingly, SBG in the mixed dentition phase (6-11 years) has become the preferred method of treatment. The most commonly used graft material is cancellous bone from the iliac crest. Recently, many researchers have investigated the use of allogeneic bone, artificial bone, and recombinant human bone morphogenetic protein, along with growth factors because of their ability to decrease donor-site morbidity. Further investigations of bone substitutes and additives will continue to be needed to increase their effectiveness and to reduce complications.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.14 no.3
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• pp.245-253
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• 1992

To evaluate the tissue response of demineralized and undimineralized xenogeneic bone-martrix graft in extraskeletal site, we prepared human bone as a implant matrix, and outbred mouse as a recipient. Before clinical application of bank bone of human in Wonkwang university, we should confirm the allogeneic bone grafts us a biologically useful bone graft substitutes, obtanined from the patients receiving oral and maxillofacial surgery. The clinical evaluation and histologic studies showed that both (demineralized and undemineralized) xenogeneic bone matrix grafts were not rejected and that they seemed to stimulate new bone formation at the transplanation site. Undemineralized xenogeneic bone marb6 grafts showed minimal bone induction and gradual demineralization with slow resorption and showed that the differentiation of cells showing fibroblastic activity adjacent to the sop tissue were slowly and less frequently than demineralized bone. Characteristical differences between the demineralized and undemineralized matrix were the appearance of foreign body giant cells (multinucleated giant cells) and the evidence of sloe resorption in undemineralized bone matrix.

• IMMUNE NETWORK
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• v.5 no.3
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• pp.163-171
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• 2005

Background: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary me tastasis model. Methods: B16F10 melanoma cells $(1{\timeS}10^5/mouse)$ were inoculated intra venously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs $(1{\times}10^6/mouse)_{[CGP1]}$ were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. Results: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: $2.7{\pm}0.3,\;0.7{\pm}0.3\;and\;0.3{\pm}0.2$ for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-${\gamma}$ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: $44.97{\pm}10.31,\;1787.94{\pm}131.18,\;1257.15{\pm}48.27$, w/CloneM3 lysate: 0, $1591.13{\pm}1.83,\;1460.47{\pm}86.05pg/ml$ for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC ($8.9{\pm}_{[CGP2]}0.1,\;11.6{\pm}0.8\;and\;12.6{\pm}0.7%$ specific NK activity for saline, B-DC and C-DC treated group, respectively). Conclusion: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.

• The Journal of the Korean bone and joint tumor society
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• v.17 no.2
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• pp.73-78
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• 2011

Purpose: This study was aimed to evaluate the result of inlay cortical strut bone grafts for large cysts or cavitary bone lesions in long bones. Materials and Methods: Seven patients with large cyst or cavitary bony lesions were managed with curettage, allogeneic inlay cortical strut and cancellous bone grafts. Additional plate and screw fixations were performed in 6 patients. There were three SBCs, two FDs with secondary ABC changes, one FD and one post-cement spacer removal state. Three of them had pathologic fractures. Progression of bone healing and mechanical support and functional result were evaluated. The mean follow-up period was 25.4 months. Results: Incorporations into host bones were progressed in all, average 4.2 months in six metaphyseal regions and 5.8 months in five diaphyseal regions respectively. Full structural supports were achieved in all except one patient without any additional procedures. No allograft-related complication was developed. Mean functional score according to the MSTS criteria was 29.6 at last follow up. Conclusion: Inlay cortical strut graft provided additional mechanical stability and bone stock for screw purchase in large cyst or cavitary defects of long bones, which allow early mobilization and excellent functional outcome.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.4
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• pp.405-411
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• 1991

To determine the sterility of the prepared allogeneic bone of the human, culture of the allografts prior to implantation was performed on fresh-frozen and freeze-dried bone. Before the use of allografts to the patients, it must be confirmed about the sterility, cellular cytotoxicity, immune reaction, and osteoinductive potential as a biomaterials. Oral and maxillofacial surgeons demand for allograft bone will be increased in the future. Wonkwang Bone Bank attempted to meet this demand, has performed series of experimental study on the allograft bone of the Koreans to evaluate the physical and chemical suitability of the bone since the surgeons applications will have broadened from benign cystic lesions to fracture malunions and non-unions, large segmental defects, and whole-bone allorgrafts after tumor surgery. The results obtained were as follows: 1. Freeze-drying(FD) only shoed some bactericidal effects of the normal and osteo bone but in cases of performing EO gas sterilization, the FD effects was not clear. 2. The fact that FD has little effect than the EO gas sterilization on normal bone postulated that the presence of microbiota may be due to an operation and bone processing procedure. 3. FD and EO gas sterilization had a remarkable effect on the osteo bone. 4. The sterilization effect were EO gas, Freeze-drying, Fresh-Frozen with descending order. But all sterilization method were not complete to preserve and implant allograft bone. We are now performing further continuous study on the radiation and chemical sterilization procedure to make safe and complete allograft bone.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.199-203
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• 2006

Background: Eckol purified from Ecklonia cava, a brown alga has been known to have cytoprotective effects on some cell lines against oxidants and ionizing radiation. However, there is no study about the effects of eckol on immune cells. Methods: Bone marrow (BM)-derived dendritic cells (DCs) were used to demonstrate the immunomodulatory effects of eckol on DCs, such as viability, the expression of surface markers, allogeneic stimulating capacity using MTI, flow cytometric, $^3H$-thymidine incorporation assay. Results: Eckol did protect DCs against cytokine withdrawal-induced apoptosis in a concentration dependent manner based on MTT assay. And also, it increased the expression of MHC class II and CD86 (B7.2) molecules, maturation markers, on the surface of viable DCs gated in FACS analysis. Furthermore, eckol-treated DCs stimulated the proliferation of allogeneic $CD4^+$ T lymphocytes compared to imDCs in $^3H$-thymidine incorporation assay. $CD4^+$ T lymphocytes activated with eckol-treated DCs produced the larger amount of IFN-${\gamma}$ and IL-4 than those cells with imDCs. Conclusion: Taken together, we demonstrate in this study that eckol, a pure compound of Ecklonia cava, may modulate the immune responses through the phenotypic and functional changes of DCs.

• IMMUNE NETWORK
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• v.7 no.2
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• pp.95-100
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• 2007

Background: A red seaweed, Callophyllis japonica has been traditionally eaten in the oriental area. In a recent study, it has been demonstrated that the ethanol extract of C. japonica have antioxidant activity. However, there are few studies about the effects of C. japonica on the function of immune cells. We investigated the immunomodulatory effects of C. japonica on the function of dendritic cells, the potent antigen-presenting cells. Methods: Bone marrow-derived dendritic cells (DCs) were used and the viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and trypan blue exclusion test. Cytokine and nitric oxide (NO) levels were determined by using ELISA and Griess reagent, respectively. The expression levels of DC surface markers were measured by flow cytometric analysis. Results: C. japonica ethanol extract did not significantly affect the DCs viability and the IL-12 production from DCs, irrespective of the presence of lipopolysaccharide (LPS). In addition, it did not significantly change the expression of DC surface markers. However, C. japonica ethanol extract significantly inhibited the LPS-induced NO production and also increased the proliferation of allogeneic lymphocytes activated by DCs. Conclusion: Our data suggests that C. japonica ethanol extract enhances the proliferation of allogeneic lymphocytes activated by DCs which is associated with inhibition of NO production from DCs induced by LPS.