• IMMUNE NETWORK
• /
• 제4권2호
• /
• pp.88-93
• /
• 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
• /
• 제20권1호
• /
• pp.63-67
• /
• 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
• /
• 제50권6호
• /
• pp.519-523
• /
• 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
• /
• 제44권3호
• /
• pp.188-193
• /
• 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
• /
• 제14권3호
• /
• pp.245-253
• /
• 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
• /
• 제5권3호
• /
• pp.163-171
• /
• 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.

• 대한골관절종양학회지
• /
• 제17권2호
• /
• pp.73-78
• /
• 2011

목적: 사지 장골의 거대한 골 낭종이나 소파술 후 남은 골 결손부에 시행한 "내재형 피질 지주골 이식술"의 치료결과를 평가하였다. 대상 및 방법: 사지 장골의 거대한 골 낭종이나 소파술 후 남은 골 결손부에 대하여 내재형 동종 피질 지주골과 동종 망상골 이식술을 시행한 7예를 대상으로 하였다. 6예에서는 추가적인 금속판 내고정술이 시행되었다. 원발병소는 단순 골낭종이 3예, 섬유성 이형성증에서 속발된 동맥류성 골낭종이 2예, 이전에 수술한 골시멘트를 제거한 후 남은 골 결손이 1예, 섬유성 이형성증이 1예였다. 3예에서는 최초 내원시 병적 골절이 동반되어 있었다. 골 융합의 진행, 생역학적 지지기능 및 기능적 결과를 평가하였으며 평균 추시 기간은 25.4개월이었다. 결과: 전예에서 이식된 동종 피질 지주골은 숙주골과 융합되었으며 6예의 골간단부에서는 평균 4.2개월에, 5예의 골간부에서는 평균 5.8개월에 융합되었다. 부가적인 수술 등의 조치없이 7예 중 6예에서 생역학적 지지가 가능하였으며 동종골 이식과 직접 관련된 합병증은 발생하지 않았다. 최종 추시시 기능적 평가상 평균 29.6으로 우수한 결과를 보였다. 결론: 거대한 골 낭종이나 소파술 후 남은 골 결손부에 시행한 내재형 피질 지주골 이식술은 추가적인 생역학적 안정성과 나사못 고정의 골지주판을 제공하여 조기거동과 우수한 기능적 결과를 가능하게 하였다.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제13권4호
• /
• pp.405-411
• /
• 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
• /
• 제6권4호
• /
• pp.199-203
• /
• 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
• /
• 제7권2호
• /
• pp.95-100
• /
• 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.