A novel, ring-connected stent versus conventional GI stents: comparative study of physical properties and migration rates in a canine colon obstruction model.

BACKGROUND: Migration of stents is one of the most common adverse events in covered stent placement in GI tract obstruction. OBJECTIVE: To compare physical property and migration rates in a canine colon obstruction model among a novel stent and conventional stents. DESIGN: Comparative physical test and animal study. SETTING: Medical device testing laboratory and animal laboratory. SUBJECTS: Mongrel dogs (N=26). INTERVENTIONS: Surgical colon obstruction followed by placement of a novel (n=13) or conventional (n=13) stent. MAIN OUTCOME MEASUREMENTS: Physical properties, migration, and adverse events. RESULTS: The novel stent showed better flexibility, as in a physical test of longitudinal compressibility and axial force, than did conventional stents, and it withstood the fatigue test for 10 days. In terms of radial force and tensile strength, the novel stent showed the same or better results than conventional stents. In a canine colon obstruction model, the migration rate of a novel stent was significantly lower than that of a conventional stent (2/13, 15.4% vs 8/13, 61.5%; P=.008). LIMITATIONS: Animal study of limited size. CONCLUSION: The novel, ring-connected stent is more flexible and more resistant to migration than the conventional stents.

Therapeutic effects of human amniotic epithelial stem cells in Niemann-Pick type C1 mice.

BACKGROUND AIMS: Niemann-Pick disease type C1 (NPC) is an autosomal recessive cholesterol-storage disorder characterized by liver dysfunction, hepatosplenomegaly and progressive neurodegeneration. Thus far, studies of NPC mice have been performed mainly to study the brain and neurodegeneration, because degeneration in the brain was known as the primary cause of death in NPC mice. However, NPC is a systemic disease; therefore the purpose of this study was to find the possibility of a general therapeutic effect by applying and tracking transplanted human amniotic epithelial stem cells (hAESC) in NPC mice. METHODS: hAESC were administered to NPC homozygous (NPC(-/-)) mice via intravenous injection from 5 weeks of age; each recipient received 5 × 10(5) cells every other week. The body weight of each of the mice was measured every week, and the survival and state of each mouse was evaluated every day. The weight of the organs was measured, and serum chemistry, histology and the intensity of Filipin staining were evaluated. RESULTS: The effect of cell transplantation was to extend the life span and reduce the rapid loss of weight. Moreover, alleviation of tissue damage was observed more in hAESC-treated NPC(-/-) mice than in non-treated NPC(-/-) mice. Cholesterol deposition was reduced after transplantation, and the relative weight of the liver was also decreased. CONCLUSIONS: These data show that hAESC could delay the degeneration caused by fatal genetic disorders such as NPC. This study presents the prospect of relief of precipitous disease progression and the therapeutic possibility of applying hAESC to fatal genetic disorders.

Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice.

BACKGROUND: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. OBJECTIVES: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. METHODS: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patient-derived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. RESULTS: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. CONCLUSIONS: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

Double-filtered leukoreduction as a method for risk reduction of transfusion-associated graft-versus-host disease.

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GvHD) is caused by leukocytes, specifically T cells within a transfused blood product. Currently, the prevention of transfusion-associated graft-versus-host disease is performed by irradiation of blood products. With a sufficient reduction of leukocytes, the risk for TA-GvHD can be decreased. With consistent advances in current state-of-the-art blood filters, we herein propose that double filtration can sufficiently reduce leukocytes to reduce the risk for TA-GvHD. MATERIALS: Thirty RBC concentrates were filtered with leukocyte filters, followed by storage at 1-6 oC for 72 hours, and then a second filtration was performed. Residual leukocytes in the double-filtered RBC units (n = 30) were assessed with flow cytometric methods, and an additional assay with isolated peripheral blood mononuclear cells (PBMCs) (n = 6) was done by both flow cytometric methods and an automated hematology analyzer. Quality of the RBCs after filtration was evaluated by hematological and biochemical tests. In vitro T cell expansion was performed using anti-CD3/CD28-coated Dynabeads or anti-CD3 (OKT3). In vivo experiment for GvHD was performed by using NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. RESULTS: Double-filtered blood products showed residual leukocyte levels below detection limits, which calculated to be below 1200-2500 cells per blood unit. In vitro expansion rate of T cells showed that 6x103 and 1x103 cell-seeded specimens showed 60.8±10.6 fold and 10.2±9.7-fold expansion, respectively. Cell expansion was not sufficiently observed in wells planted with 1x102 or 10 cells. In vivo experiments showed that mice injected with 1x105 or more cells cause fatal GvHD. GvHD induced inflammation was observed in mice injected with 1x104 or more cells. No evidence of GvHD was found in mice injected with 103 cells. CONCLUSIONS: Our study suggests that additional removal of contaminating lymphocytes by a second leukodepletion step may further reduce the risk for TA-GvHD.

In vivo verification of regional hyperthermia in the liver.

PURPOSE: We performed invasive thermometry to verify the elevation of local temperature in the liver during hyperthermia. MATERIALS AND METHODS: Three 40-kg pigs were used for the experiments. Under general anesthesia with ultrasonography guidance, two glass fiber-optic sensors were placed in the liver, and one was placed in the peritoneal cavity in front of the liver. Another sensor was placed on the skin surface to assess superficial cooling. Six sessions of hyperthermia were delivered using the Celsius TCS electro-hyperthermia system. The energy delivered was increased from 240 kJ to 507 kJ during the 60-minute sessions. The inter-session cooling periods were at least 30 minutes. The temperature was recorded every 5 minutes by the four sensors during hyperthermia, and the increased temperatures recorded during the consecutive sessions were analyzed. RESULTS: As the animals were anesthetized, the baseline temperature at the start of each session decreased by 1.3℃ to 2.8℃ (median, 2.1℃). The mean increases in temperature measured by the intrahepatic sensors were 2.42℃ (95% confidence interval [CI], 1.70-3.13) and 2.67℃ (95% CI, 2.05-3.28) during the fifth and sixth sessions, respectively. The corresponding values for the intraperitoneal sensor were 2.10℃ (95% CI, 0.71-3.49) and 2.87℃ (1.13-4.43), respectively. Conversely, the skin temperature was not increased but rather decreased according to application of the cooling system. CONCLUSION: We observed mean 2.67℃ and 2.87℃ increases in temperature at the liver and peritoneal cavity, respectively, during hyperthermia. In vivo real-time thermometry is useful for directly measuring internal temperature during hyperthermia.