Background and Objectives: The colonic epithelial layer is a complex structure consisting of multiple cell types that regulate various aspects of colonic physiology, yet the mechanisms underlying epithelial cell differentiation during development remain unclear. Organoids have emerged as a promising model for investigating organogenesis, but achieving organ-like cell configurations within colonic organoids is challenging. Here, we investigated the biological significance of peripheral neurons in the formation of colonic organoids. Methods: and Results: Colonic organoids were co-cultured with human embryonic stem cell (hESC)-derived peripheralneurons, resulting in the morphological maturation of columnar epithelial cells, as well as the presence of enterochromaffin cells. Substance P released from immature peripheral neurons played a critical role in the development of colonic epithelial cells. These findings highlight the vital role of inter-organ interactions in organoid development and provide insights into colonic epithelial cell differentiation mechanisms. Conclusions Our results suggest that the peripheral nervous system may have a significant role in the development ofcolonic epithelial cells, which could have important implications for future studies of organogenesis and disease modeling.

No abstract available.
Child* ; Humans

BACKGROUND AND OBJECTIVES: MicroRNA 145 is known to be responsible for cellular proliferation, and its enhanced expression reportedly inhibits the retardation of vascular smooth muscle cell growth specifically. In this study, we developed a microRNA 145 nanoparticle immobilized, hyaluronic acid (HA)-coated stent. MATERIALS AND METHODS: For the gene therapy, we used disulfide cross-linked low molecular polyethylenimine as the carrier. The microRNA 145 was labeled with YOYO-1 and the fluorescent microscopy images were obtained. The release of microRNA 145 from the stent was measured with an ultra violet spectrophotometer. The downstream targeting of the c-Myc protein and green fluorescent protein was determined by Western blotting. Finally, we deployed microRNA 145/ssPEI nanoparticles immobilized on HA-coated stents in the balloon-injured external iliac artery in a rabbit restenosis model. RESULTS: Cellular viability of the nanoparticle-immobilized surface tested using A10 vascular smooth muscle cells showed that MSN exhibited negligible cytotoxicity. In addition, microRNA 145 and downstream signaling proteins were identified by western blots with smooth muscle cell (SMC) lysates from the transfected A10 cell, as the molecular mechanism for decreased SMC proliferation that results in the inhibition of in-stent restenosis. MicroRNA 145 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis at the post-implantation. We investigated the qualitative analyses of in-stent restenosis in the rabbit model using micro-computed tomography imaging and histological staining. CONCLUSION: MicroRNA 145-eluting stent mitigated in-stent restenosis efficiently with no side effects and can be considered a successful substitute to the current drug-eluting stent.
Blotting, Western ; Cell Proliferation ; Drug-Eluting Stents ; Genetic Therapy ; Hyaluronic Acid ; Iliac Artery ; MicroRNAs* ; Microscopy ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Nanoparticles ; Polyethyleneimine ; Stents* ; Viola

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days –8 to –5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m2) was administered once daily for 6 consecutive days from days –8 to –3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days –4 to –2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.
Antilymphocyte Serum ; Bone Marrow Transplantation* ; Bone Marrow* ; Busulfan* ; Granulomatous Disease, Chronic* ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Transplantation Conditioning

PURPOSE: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. Due to its extreme rarity, most of the available data are based on retrospective case series. To add to the current knowledge of this disease, we reviewed the patients treated for extra-cranial MRT in our institute. MATERIALS AND METHODS: A retrospective medical record review was conducted on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children's Hospital between January 2003 and May 2013. RESULTS: Eleven patients (7 boys, 4 girls) were diagnosed with extra-cranial MRT at a median age of 9 months old. INI1 staining was important in the pathological confirmation. Six patients (55%) had renal MRT and five (45%) had soft tissue MRT. Five patients (45%) had metastases at diagnosis. All patients underwent chemotherapy, eight patients (73%) underwent surgery, six patients (55%) received therapeutic radiotherapy, and four patients (36%) underwent high dose chemotherapy with autologous stem cell rescue (HDCT/ASCR) with melphalan, etoposide, and carboplatin. Five patients (45%) died of disease following progression (n=3) or relapse (n=2), however, there was no treatment related mortality. The overall survival of the cohort was 53.0% and the event-free survival was 54.5% with a median follow-up duration of 17.8 months (range, 2.3 to 112.3 months). CONCLUSION: Extra-cranial MRT is still a highly aggressive tumor in young children. However, the improved survival of our cohort is promising and HDCT/ASCR with melphalan, etoposide, and carboplatin may be a promising treatment option.
Carboplatin ; Child* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Etoposide ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; Medical Records ; Melphalan ; Mortality ; Neoplasm Metastasis ; Radiotherapy ; Recurrence ; Retrospective Studies ; Rhabdoid Tumor* ; Seoul ; Soft Tissue Neoplasms ; Stem Cells

Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, splenomegaly, jaundice, and pathologic findings of hemophagocytosis in bone marrow or other tissues such as the lymph nodes and liver. Pleocytosis, or the presence of elevated protein levels in cerebrospinal fluid, could be helpful in diagnosing HLH. However, the pathologic diagnosis of the brain is not included in the diagnostic criteria for this condition. In the present report, we describe the case of a patient diagnosed with HLH, in whom the brain pathology, but not the bone marrow pathology, showed hemophagocytosis. As the diagnosis of HLH is difficult in many cases, a high level of suspicion is required. Moreover, the pathologic diagnosis of organs other than the bone marrow, liver, and lymph nodes may be a useful alternative.
Biopsy* ; Bone Marrow ; Brain Diseases ; Brain* ; Central Nervous System ; Cerebrospinal Fluid ; Diagnosis ; Fever ; Humans ; Jaundice ; Leukocytosis ; Liver ; Lymph Nodes ; Lymphohistiocytosis, Hemophagocytic* ; Pathology ; Splenomegaly

A 1.1 year old boy was admitted to the Seoul National University Children's Hospital because of incidental findings of hepatosplenomegaly, skin lesion and multiple intra- abdominal lymphadenopathies. Anemia and thrombocytopenia were found based on the initial complete blood count (CBC) measurements. Because of bicytopenia and hepatosplenomegaly, bone marrow examination was performed which revealed hypercellular marrow with increased monocytes and granulopoiesis. The hemoglobin F level was high for his age, and monocyte production was increased. The patient was diagnosed with juvenile myelomonocytic leukemia at the age of 1.2 years. Chemotherapy with cytarabine, etoposide, vincristine, and isotretinoin was initiated. After 6 cycles of chemotherapy, the CBC normalized. He underwent double cord blood transplantation (dCBT), but chimerism studies showed autologous recovery. However, he did not show relapse during the 5 years post-transplant during which he received isotretinoin. He is surviving disease-free 9 years after dCBT.
Anemia ; Blood Cell Count ; Bone Marrow ; Bone Marrow Examination ; Chimerism ; Cytarabine ; Drug Therapy ; Etoposide ; Fetal Blood ; Fetal Hemoglobin ; Humans ; Incidental Findings ; Isotretinoin ; Leukemia, Myelomonocytic, Juvenile ; Male ; Monocytes ; Recurrence ; Seoul ; Skin ; Thrombocytopenia ; Vincristine

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an aggressive malignancy with a poor prognosis. DSRCT is a rare disease, and therefore a standard treatment regimen has not been established. In this study, we reviewed the clinical characteristics and treatment outcomes of pediatric DSRCT patients.METHODS: We retrospectively reviewed the medical records of 5 DSRCT patients (2 boys, 3 girls) that were diagnosed and treated with DSRCT at Seoul National University Children's Hospital from January 1999 to January 2015.RESULTS: The median age at diagnosis was 11 years 5months (range 4 years 10 months-17 years 2 months). The most frequent symptoms were abdominal pain (60%). The primary sites were gastrointestinal tract, bladder, and omentum, and the involved sites were the liver, gastrointestinal tract, bladder and bone. Three patients had multiple metastases at diagnosis. Two patients underwent upfront surgical excision of primary tumor, and the remaining 3 patients received neo-adjuvant chemotherapy after the diagnosis was confirmed by using needle biopsy. Combination chemotherapy was administered to all patients in addition to radiotherapy (median dose 45 Gy, range 17.5-54 Gy). Four patients showed disease progression or relapse, resulting in a 20% overall survival rate. At the time of analysis, one patient is alive. She had localized disease at the time of diagnosis and were treated with upfront surgery, chemotherapy, and high-dose chemotherapy with autologous stem cell transplantation and radiotherapy.CONCLUSION: Patients with DSRCT have a poor prognosis, even after multimodal treatment. Further studies are needed to determine the prognostic factors of DSRCT.
Abdominal Pain ; Biopsy, Needle ; Combined Modality Therapy ; Desmoplastic Small Round Cell Tumor ; Diagnosis ; Disease Progression ; Drug Therapy ; Drug Therapy, Combination ; Gastrointestinal Tract ; Humans ; Korea ; Liver ; Medical Records ; Neoplasm Metastasis ; Omentum ; Pediatrics ; Prognosis ; Radiotherapy ; Rare Diseases ; Recurrence ; Retrospective Studies ; Seoul ; Stem Cell Transplantation ; Survival Rate ; Treatment Outcome ; Urinary Bladder

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but devastating complication in patients who undergo hematopoietic stem cell transplantation (SCT). However, the optimal treatment strategy for TA-TMA is unclear. We report a rare case of TA-TMA in a 39-month-old boy who underwent tandem autologous SCT (autoSCT) for high-risk medulloblastoma. TA-TMA developed 64 days after the second autoSCT with microangiopathic hemolytic anemia, fever, renal impairment, acute respiratory distress syndrome and posterior reversible encephalopathy syndrome. The patient recovered after plasmapheresis and methylprednisolone therapy. He had mild to moderate deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13). The patient's clinical course would suggest that plasmapheresis and methylprednisolone therapy could be a treatment option for TA-TMA. Early intervention is needed to aid the recovery of the patient who is suspected for TA-TMA.
Anemia, Hemolytic ; Child, Preschool ; Early Intervention (Education) ; Fever ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Medulloblastoma ; Methylprednisolone ; Pediatrics ; Plasmapheresis ; Posterior Leukoencephalopathy Syndrome ; Respiratory Distress Syndrome, Adult ; Stem Cell Transplantation ; Thrombospondins ; Thrombotic Microangiopathies

BACKGROUND: Nasopharyngeal carcinoma (NPC) is very rare in children and adolescents. The aim of this study was to evaluate clinical characteristics and treatment outcomes of pediatric NPC.METHODS: Medical records of 9 patients treated for NPC at the Seoul National University Children's Hospital between 1988 and 2012 were analyzed retrospectively.RESULTS: The median age at diagnosis was 11 years (range, 9-13 years). One patient had stage II disease, 3 had stage III disease, and 5 had stage IV disease. The histologic subtypes were undifferentiated carcinoma and squamous cell carcinoma in 7 and 2 patients, respectively. All patients were initially treated with cisplatin (100 mg/m2 intravenous [IV] every 4 weeks for 4-6 months), bleomycin (15 unit/m2 IV every 1 weekx7), and fluorouracil (1,000 mg/m2 IV every 4 weeks for 1 year). Eight patients received radiotherapy with doses of 45-59.4 Gy at the primary site and neck nodes. Seven patients (77.8%) achieved complete remission, 1 (11.1%) achieved partial remission, and 1 (11.1%) showed disease progression. Six patients developed fluorouracil-related neurotoxicity; the regimen was changed to cisplatin, epirubicin, and bleomycin in five of the 6 patients. One patient died of progressive disease without responding to treatment. Treatment-related mortality occurred in 1 patient owing to septic shock. Secondary osteosarcoma developed in 1 patient 6 years after treatment. The overall survival was 77.8%, with a median follow-up of 40.8 months (range, 4.5-287.6 months).CONCLUSION: Children and adolescents with advanced NPC treated with combined chemotherapy and radiotherapy have a good survival rate.
Adolescent ; Bleomycin ; Carcinoma ; Carcinoma, Squamous Cell ; Chemoradiotherapy ; Child ; Cisplatin ; Diagnosis ; Disease Progression ; Drug Therapy ; Epirubicin ; Fluorouracil ; Follow-Up Studies ; Humans ; Korea ; Medical Records ; Mortality ; Nasopharyngeal Neoplasms ; Neck ; Osteosarcoma ; Pediatrics ; Radiotherapy ; Retrospective Studies ; Seoul ; Shock, Septic ; Survival Rate