• International Journal of Stem Cells
• /
• v.15 no.4
• /
• pp.395-404
• /
• 2022

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a common, frequently-occurring disease and poses a major health concern. Unfortunately, there is current no effective treatment for COPD, particularly emphysema. Recently, experimental treatment of COPD using mesenchymal stem cells (MSCs) mainly focused on bone marrow-derived MSCs (BM-MSCs). Human umbilical cord-derived MSCs (hUC-MSCs) have more advantages compared to BM-MSCs. However, studies on the role of hUC-MSCs in management of COPD are limited. This study sought to explore the role of hUC-MSCs and its action mechanisms in a rat model of VEGF receptor blocker SU5416-injured emphysema. Methods and Results: hUC-MSCs were characterized by immunophenotype and differentiation analysis. Rats were divided into four groups: Control, Control+MSC, SU5416 and SU5416+MSC. Rats in model group were administered with SU5416 for three weeks. At the end of the second week after SU5416 administration, model group were infused with 3×10⁶ hUC-MSCs through tail vein. After 14 days from hUC-MSCs transplantation, rats were euthanized and data were analyzed. HE staining and mean linear intercepts showed that SU5416-treated rats exhibited typical emphysema while emphysematous changes in model rats after hUC-MSCs transplantation disappeared completely and were restored to normal phenotype. Furthermore, hUC-MSCs inhibited apoptosis as shown by TUNEL and Western blotting. ELISA and Western blotting showed hUC-MSCs rescued VEGF-VEGFR2-AKT pathway in emphysematous lungs. Conclusions: The findings show that hUC-MSCs effectively repair the emphysema injury. This study provides the first evidence that hUC-MSCs inhibit apoptosis via rescuing VEGF- VEGFR2-AKT pathway in a rat model of emphysema.

• The Journal of the Korean bone and joint tumor society
• /
• v.11 no.1
• /
• pp.54-61
• /
• 2005

Purpose: The granulocytic sarcoma which developed in leukemic patients are quite rare and it will have bad prognosis, but it's tumor pathogenesis and also their treatment are not yet established. Through this study we have tried to know their clinical course, prognosis and their end result of recent treatment. Material and Methods: Total 20 patients of granulocytic sarcoma which were developed in total 2,197 leukemic patients from April, 1998 to September, 2004 were treated at the leukemic center and the orthopaedic department of St. Mary's hospital, Catholic University of Korea, and followed them for 1~78 months(average 18 months). Results: Total 20 cases of granulocytic sarcoma was found in 14 cases of total 1,331 acute myelocytic leukemic patients(AML), 4 cases of total 744 of chronic myelocytic leukemic patients(CML), and only one case in total 122 of acute biphenotype of leukemia. And so their occurrence rate in leukmic patients are actually 0.91%, total 20 cases of granulocytic sarcoma in total 2,197 leukemic patients at same period. Their ages are average 28.3 years(4~52 years), and male are predominant(13 cases) than female(7 cases). Single involvement was found in 11 cases but multiple lesions are in 9 cases, and spine, brain, extremities, chest, and pelvic bone are involved in frequency. The granulocytic sarcoma was developed in various stages of the leukemia, ie, 8 cases in complete remission of leukemia, and 12 cases in the treatment process of AML. The pathohistologic evaluation of granulocytic sarcoma was done in 6 cases which was developed in their extremities, and confirmed numerous immature myeloblasts and lymphocytes mixed. The treatment of these granulocytic sarcoma was mainly limited for the treatment of leukemia by Glivac and massive steroid therapy(19cases) and also combined with the bone marrow transplantation(13 cases), but radiation therapy with average 3,500 rads in 15 cases out of total 20 sarcomas was also done, and followed them for average 17.5 months after development of granulocytic sarcomas. Finally their prognosis was so bad that 12 patients(60%) out of total 20 granulocytic sarcoma were dead in 6.5 months after sarcoma developed and we found the granulocytic sarcoma was more fatal if they are developed during the process of CML(mortality: 100%(4/4cases). Conclusion: The prognosis of granulocytic sarcomas in leukemic patients are quite fatal, and much more studies for their pathogenesis and ways of treatment should be performed continuously.

• Journal of Haehwa Medicine
• /
• v.21 no.1
• /
• pp.11-21
• /
• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• Clinical and Experimental Pediatrics
• /
• v.45 no.7
• /
• pp.912-916
• /
• 2002

Cord blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution. The number of umbilical cord blood transplants is increasing worldwide. In this a case 15-month-old boy with acute myeloid leukemia was treated with umbilical cord blood transplant from an HLA-3 loci mismatched unrelated donor. Granulocyte recovery greater than $500/mm^3$ occurred at day 49, and the platelet recovered greater than $20,000/mm^3$ independent of transfusion at day 81 after stem cell infusion.

• Journal of Veterinary Clinics
• /
• v.28 no.4
• /
• pp.394-398
• /
• 2011

Mesenchymal stem cells (MSC) are pluripotent cells that can be found in umbilical cord blood from new borne babies as well as placenta, bone marrow, adipose tissue, amniotic fluid, muscle, et al. MSC are capable of renewing themselves without differentiation in long-term culture, also can be differentiated into various tissues under specific condition. Formulating a cryopreservation protocol for the MSC is required because these cells cannot survive for long periods under in vitro culture conditions and a new formulation of harmless cryoprotectant is needed for the direct injection of MSC into patients. The undifferentiated MSC were frozen with a vitrification solution of 40% ethylene glycol, 20% Ficoll-70 and 0.3M sucrose. The survival rate after thawing and their proliferation rate were examined and compared with slow rate cooling methods using dimethylsulfoxide (DMSO). The vitrification method showed high survival rate after thawing and proliferation capacity comparable to DMSO. It can be suggested that ultra-rapid cooling method by vitrification is reliable methods for long term preservation of MSC and the vitrification solution with ethylene glycol, Ficoll-70 and sucrose will be more beneficially used for direct transplantation of MSC into patients than DMSO solution.

• Archives of Pharmacal Research
• /
• v.29 no.12
• /
• pp.1147-1153
• /
• 2006

Mizoribine (MZR) has been shown to possess immunosuppressive activity that selectively inhibits the proliferation of lymphocytes by interfering with inosine monophosphate dehydrogenase. The efficacy of MZR is not only in patients who have had renal transplantation, but also in patients with rheumatoid arthritis (RA), lupus nephritis, and primary nephritic syndrome. Because the exact mechanism of its immunosuppressive action is not clear, the object of this study was to examine the ability of MZR to regulate the antigen presenting cells (APCs), dendritic cells (DCs). In this work, we tested whether MZR ($1{\sim}10\;{\mu}g/mL$) could inhibit the cross-presentation of DCs. DC2.4 cells ($H-2K^{b}$) or bone marrow-derived DCs (BM-DCs) generated from BM cells of C57BL/6 mouse ($H-2K^{b}$) were cultured in the presence of MZR with OVA-microspheres, and the amount of OVA peptide-class I MHC complexes was measured by a T cell hybridoma, B3Z, that recognizes OVA (257-264 : SIINFEKL)-$H-2K^{b}$ complex and expresses-galactosidase. MZR profoundly inhibited the expression of SIINFEKL-$H-2K^{b}$ complexes. This inhibitory activity of MZR appeared to affect the phagocytic activity of DCs. MZR also decreased IL-2 production when we examined the effects of MZR on $CD4^{+}$ T cells. These results provide an understanding of the mechanism of immunosuppressive activity of MZR on the inhibition of MHC-restricted antigen presentation and phagocytic activity in relation to their actions on APCs.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.1
• /
• pp.51-55
• /
• 2007

In the average adult with a normal immune state, Epstein-Barr virus pneumonia is very rare, especially in the form of interstitial lung disease. According to recent studies, the Epstein-Barr virus is also associated with lymphocytic interstitial pneumonia, AIDS and Langerhans cell histiocytosis, but not with sarcoidosis. BOOP is caused by lung injury due to an infection or drug intoxication, and is related to connective tissue disease or bone marrow transplantation, but is sometimes idiopathic. We experienced a patient with symptoms and signs of interstitial lung disease, with confirmed BOOP and EBV ingection from an open lung biopsy and serologic examination, respectively Herein, this case is reported, with a review of the literature.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.27 no.6
• /
• pp.523-527
• /
• 2005

Allograft donations are commonly found to be contaminated. The most of tissue banks has promoted the use of ionizing radiation for the sterilization of biological tissues. The potential for transmission of human infectious diseases and contamination of microorganism has created serious concern for the continued clinical use of hard and soft-tissue allografts. Tissue banks have employed 15-25kGy for sterilization of hard and tendon allografts, which, according to the national standards, approaches the level at which the tissue quality is adversely affected for transplantation. The donations of allogeneic tissues to the Korea Tissue Bank over a 2-year period were reviewed, and the incidence and bacteriology of contamination were detailed. Clinical outcomes were determined for donors who had positive cultures at the time of retrieval and during the processing and they were compared with those of post sterilization. After exposure of the frozen block bone to 25kGy and the processed tissues to 15kGy of gamma irradiation, the authors were able to demonstrate complete inactivation of the bacteria. The aim of this study was to obtain the effects of gamma irradiation and the irradiation dose according to the type of tissue, through conventional microbiologic test without on influence of biocompatibility in allografts. The contamination rate after the final irradiation sterilization is 0% in the processed allografts. This may be due to the fact that the gamma radiation and processing steps are effective to control contamination.

• Journal of the korean academy of Pediatric Dentistry
• /
• v.32 no.3
• /
• pp.437-443
• /
• 2005

Dilaceration is most common in maxillary central incisor. Impaction by dilacerated tooth cause orthodontic problem such as tilting of adjacent tooth, midline deviation. Dilaceration is caused by trauma, cyst, other origin and tooth shape, degree of root curvature, location in the alveolar bone, ability of spontaneous eruption should be considered whether treat or not. Labially and lingually dilacerated tooth is difficult to spontaneous eruption. Thus, Prosthetic treatment alternative with extraction, auto transplantation, orthodontic traction with surgical exposure is included within the treatment alternative. These cases are about impacted central incisor with dilacerated root. We use closed eruption technique and guide impacted tooth into normal position by orthodontic traction.

• Biomolecules & Therapeutics
• /
• v.28 no.1
• /
• pp.34-44
• /
• 2020

Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.