• Journal of Veterinary Science
• /
• v.21 no.1
• /
• pp.9.1-9.15
• /
• 2020

Regenerative therapy holds great promise in the development of cures of some untreatable diseases such as cardiovascular diseases, and pluripotent stem cells (PSCs) including induced PSCs (iPSCs) are the most important regenerative seed cells. Recently, differentiation of human PSCs into functional tissues and cells in vitro has been widely reported. However, although porcine reports are rare they are quite essential, as the pig is an important animal model for the in vitro generation of human organs. In this study, we reprogramed porcine embryonic fibroblasts into porcine iPSCs (piPSCs), and differentiated them into cluster of differentiation 31 (CD31)-positive endothelial cells (ECs) (piPSC-derived ECs, piPS-ECs) using an optimized single-layer culture method. During differentiation, we observed that a combination of GSK3β inhibitor (CHIR99021) and bone morphogenetic protein 4 (BMP4) promoted mesodermal differentiation, resulting in higher proportions of CD31-positive cells than those from separate CHIR99021 or BMP4 treatment. Importantly, the piPS-ECs showed comparable morphological and functional properties to immortalized porcine aortic ECs, which are capable of taking up low-density lipoprotein and forming network structures on Matrigel. Our study, which is the first trial on a species other than human and mouse, has provided an optimized single-layer culture method for obtaining ECs from porcine PSCs. Our approach can be beneficial when evaluating autologous EC transplantation in pig models.

• The Korean Journal of Medicine
• /
• v.99 no.1
• /
• pp.37-49
• /
• 2024

Background/Aims: In Korea, the incidence of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is increasing and autologous stem cell transplantation (ASCT) has improved the survival of younger patients. We explored our real-world experience with PCNSL at Asan Medical Center (AMC). Methods: We used the AMC lymphoma registry to collect patient data prospectively. We analyzed 279 patients diagnosed from 2002 until August 2019. Results: The PCNSL incidence at AMC increased progressively and comprised 7.4-8.9% of new non-Hodgkin lymphoma patients annually during the most recent 4 years. The median age was 60 years (range, 17-85) and males comprised 55%. Patients under 65 years of age (n = 183) had no significant differences in characteristics compared to those aged 65 years or over, with the exception of less occipital lobe involvement and lower beta-2 microglobulin levels. Rituximab, methotrexate, procarbazine, and vincristine (R-MPV) combination induction had the best overall response, of 95%. The median overall survival was 3.8 years with 5- and 10-year survival rates of 41.5% and 30.2%, respectively. Survival was better in younger patients and those treated with ASCT. Thiotepa, busulfan, and cytoxan (TBC) conditioning chemotherapy had better survival than other combinations. The International Extranodal Lymphoma Study Group and Memorial Sloan Kettering Cancer Center prognostic score systems were valid in this cohort. Age and performance status were independent prognostic factors. Exclusive extra-central nervous system failure occurred in six patients (5.6%) among 107 failures. Conclusions: The incidence of PCNSL is rising. R-MPV induction therapy followed by ASCT with TBC has improved the survival of young, fit PCNSL patients.

• Childhood Kidney Diseases
• /
• v.13 no.2
• /
• pp.130-137
• /
• 2009

Purpose : Stem cell transplantation (SCT) has gained worldwide acceptance as a treatment for hematologic disorders. This study was performed to evaluate the clinical characteristics and outcomes of the acute kidney injury after SCT in children. Methods : The records of 53 patients who were treated with SCT at the pediatric department of Yeungnam University Hospital between January, 1996 and April, 2009 were used as subjects. Their were divided into two groups ; 'Early renal insufficiency' (ERI, n=18) and 'Non-early renal insufficiency' (NERI, n=35). ERI had greater than 25% of drop in GFR after SCT. Results: Total 53 patients were analyzed. In cord blood SCT (n=11), ERI was 4 (36.4%) and NERI was 7 (63.6%). In bone marrow SCT (n=16), ERI was 8 (50.0%) and NERI was 8 (50.5%). In autologous peripheral blood SCT (n=26), ERI was 6 (23.1%) and NERI was 20 (76.9%). There is no difference in both groups according to kinds of SCT. GVHD was developed in 22 patients, and there is no difference in each group. Twenty two of 53 patients died. ERI was 12 (66.7%) and NERI was 10 (28.6%). Acute renal failure is most important cause of the deaths. Conclusion : Out of 53 pediatric patients who were treated with SCT, 18 patients had greater than 25% of drop in GFR. There is no difference in both groups according to kinds of SCT. GVHD was found in 22 patients and there is no relation between GVHD development and acute kideney injury.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.198-206
• /
• 2000

Background : Pulmonary complications following bonemarrow transplantation (BMT) are common and associated with a high mortality rate. We investigated the yield, safety, and impact of fiberoptic bronchoscopy (FOB) for diagnosis of postBMT pneumoniae. Methods : From May 1997 to April 2000, 56 FOBs were performed in 52 post BMT patients for clinical pneumoniae. BMT patients with respiratory symptoms and/or pulmonary infiltrates had a thoracic HRCT(high resolution computed tomography) and bronchoscopic examination including BAL (bronchoalveolar lavage), TBLB (transbronchial lung biopsy), PSB (protected specimen brush). Results : The characteristics of the subjects were as follows : 37 males, 15 females, mean age of 31.3 years(l7-45), 35 sibling donor allogenic BMTs, 15 nonrelated donor allogenic BMTs, and 2 autologous BMTs. Fiftynine percent of FOBs (33 FOBs, 31 patients) were diagnostic. Isolated pathogens included the following : 12 cytomegalovirus (CMV) (21.4 %), 7 pneumocystis carinii (PC) (12.5 %), 11 CMV with PC (19.6 %), 2 Mycobacaterium tuberculosis (3.6%), and 1 streptococcus (1.8%). Most of the radiographic findings were diffuse interstitial lesions. CMV pneumoniae had mainly diffuse interstitial nodular lesion, and PC pneumoniae had diffuse, interstitial ground glass opacity(GGO). When CMV was accompanied by PC, a combined pattern of nodular and GGO was present. Of the 56 cases (23.2%), 13 died of CMV pneumoniae (n=2), PCP (n=2),mixed infection with CMV and PC (n=3), underlying GVHD (n=1), underlying leukemia progression (n=1), or respiratory failure of unknown origin (n=4). There was no major complication by bronchoscopy. Only 3 cases developed minor bleeding and 1 episode temporary hypoxemia. Conclusion : Based on our findings, CMV and PC are the major causes of postBMT pneumoniae. In addition, BAL can be considered a safe and accurate procedure for the evaluation of pulmonary complications after BMT.

• Korean Journal of Head & Neck Oncology
• /
• v.16 no.2
• /
• pp.228-234
• /
• 2000

Objectives: Esthesioneuroblastoma is a rare malignant neoplasm that originates from the olfactory sensory cells. This tumor grows from the upper nasal cavity and ethmoid sinus and invades surrounding structures through the cribriform plate into intracranium or orbit in advanced stage. Even though there has been some controversies in determining standard treatment due to rarity of this tumor, the combination treatment of surgery and adjuvant radiation has been recommended for the locally advanced esthesioneuroblastomas. However, the recent clinical experiences of advanced cases showed that combination chemotherapy is highly effective to reduce tumor mass and improve clinical outcomes. Materials and Methods: The authors conducted a retrospective analysis of 6 esthesioneuroblastoma patients who were treated in our hospital from 1986. Results: The age of these patients was between 19 and 86 year-old. Among the 6 cases, 2 were diagnosed at stage B and 4 at stage C, according to Kadish classification. Anti-tumor treatments were performed in 5 patients. One patient refused active treatment and was lost to follow-up. Better survival outcome were observed in 3 patients who were treated with combination chemotherapy alone or combined modality treatment including chemotherapy. Conclusion: Based on our retrospective study, the combined treatment consisting of surgery, radiotherapy, and combination chemotherapy should be used to improve treatment results. And furthermore, innovative clinical approaches such as neoadjuvant chemotherapy, high-dose chemotherapy and autologous peripheral stem cell transplantation, which have been reported to have good therapeutic results, should be considered and applied actively.

• Imaging Science in Dentistry
• /
• v.45 no.1
• /
• pp.31-39
• /
• 2015

Purpose: This study was performed to evaluate the feasibility of visualizing soft tissue lesions and vascular structures using contrast-enhanced cone-beam computed tomography (CE-CBCT) after the intravenous administration of a contrast medium in an animal model. Materials and Methods: CBCT was performed on six rabbits after a contrast medium was administered using an injection dose of 2 mL/kg body weight and an injection rate of 1 mL/s via the ear vein or femoral vein under general anesthesia. Artificial soft tissue lesions were created through the transplantation of autologous fatty tissue into the salivary gland. Volume rendering reconstruction, maximum intensity projection, and multiplanar reconstruction images were reconstructed and evaluated in order to visualize soft tissue contrast and vascular structures. Results: The contrast enhancement of soft tissue was possible using all contrast medium injection parameters. An adequate contrast medium injection parameter for facilitating effective CE-CBCT was a 5-mL injection before exposure combined with a continuous 5-mL injection during scanning. Artificial soft tissue lesions were successfully created in the animals. The CE-CBCT images demonstrated adequate opacification of the soft tissues and vascular structures. Conclusion: Despite limited soft tissue resolution, the opacification of vascular structures was observed and artificial soft tissue lesions were visualized with sufficient contrast to the surrounding structures. The vascular structures and soft tissue lesions appeared well delineated in the CE-CBCT images, which was probably due to the superior spatial resolution of CE-CBCT compared to other techniques, such as multislice computed tomography.

• Molecules and Cells
• /
• v.39 no.12
• /
• pp.898-908
• /
• 2016

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.

• Journal of Veterinary Science
• /
• v.22 no.5
• /
• pp.63.1-63.14
• /
• 2021

Background: Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. Objectives: To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. Methods: Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive (IDO, PTGS2, and PTGES), inflammatory (IL6 and IL10), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. Results: cA-MSCs were expressed cell surface markers such as CD90⁺/44⁺/29⁺/45^- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. Conclusions: The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.

• Journal of Korean Foot and Ankle Society
• /
• v.25 no.4
• /
• pp.149-156
• /
• 2021

Purpose: Given the lack of definite evidence-based guidelines in clinical practice, there may be a wide variation in treatment protocols for osteochondral lesions of the talus (OLT). Based on the Korean Foot and Ankle Society (KFAS) member survey, this study aimed to report the current trends in the management of OLT. Materials and Methods: A web-based questionnaire containing 30 questions was sent to all KFAS members in September 2021. The questions were mainly related to clinical experience and preferences in diagnosis, conservative, and surgical treatments for patients with OLT. Answers with a prevalence of ≥50% of respondents were considered a tendency. Results: Sixty-two (11.3%) of the 550 surgeons queried responded to the survey. The responses to 9 (30.0%) of the total of 30 questions established a tendency. Answers exhibiting a tendency were as follows; additional diagnostic tools except for plain radiograph (magnetic resonance imaging), most common conservative treatment method (oral medication, rest), most important radiological factor in decision making for surgical treatment and method (size of the lesion, ankle instability, loose bodies), most important patient factors in decision making for surgical treatment and method (age, activity or occupation), infrequently requiring posterior arthroscopy (less than 3%), most common revision surgery for failed bone marrow stimulation procedure (osteochondral autograft transplantation [OAT]), not requiring additional procedure for donor site in OAT, the main reason for unsatisfactory result after OAT (persistent pain without radiological abnormality), no generalization of autologous chondrocyte implantation or chondrogenesis using stem cells. Conclusion: This study presents updated information on current trends in the management of OLT in Korea. Both consensus and variations in the approach to patients with OLT were revealed through this survey. Since recent biologic efforts to regenerate cartilage have been unsuccessful, further studies to identify clinical evidence would be needed.

• Pediatric Infection and Vaccine
• /
• v.21 no.2
• /
• pp.81-95
• /
• 2014

Purpose: Hematopoietic cell transplantation (HCT) recipients are vulnerable to invasive infection by Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). This study was performed to evaluate immune responses after Hib and Sp vaccination in Korean pediatric HCT recipients. Methods: Patients were prospectively enrolled at Samsung Medical Center during 2009-2011. ELISA tests to detect anti-PRP IgG antibody and antibodies to Sp serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were performed at the Center for Vaccine Evaluation and Study, Ewha Medical Research Institute. Results: Ten patients (two allogeneic, eight autologous recipients) with median age 5.4 years (range 2.7-12.2 years) were enrolled. Before Hib vaccination, 60% of patients' anti-PRP IgG titers were below $0.15{\mu}g/mL$. After vaccination, 100% of patients' anti-PRP IgG titers increased above $0.15{\mu}g/mL$ (cut-off value for detection) and $1.0{\mu}g/mL$ (cut-off value for seroprotection). For pneumococcus, in 2-5 year-old patients, pre-vaccination geometric mean concentrations (GMCs) of IgG for six serotypes (4, 6B, 9V, 14, 18C, and 23F) were below $0.35{\mu}g/mL$ and at 5 months post-vaccination GMCs of IgG for all seven serotypes increased to above $0.35{\mu}g/mL$. In patients older than 5 years, pre-vaccination GMCs of IgG for four serotypes (4, 9V, 14, and 23F) were below $0.35{\mu}g/mL$ and at 3 months post-vaccination GMCs of IgG for all seven serotypes increased to above $0.35{\mu}g/mL$. Conclusion: Most HCT recipients had low or no protective antibodies to Hib and Sp before vaccination, but showed good immune responses to protective levels after vaccination.