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Interleukin (IL)-10 exerts potent anti-inflammatory effects by suppression of both T-help (Th) 1 and Th2 cells. Previous studies have reported that IL-10 can ameliorate various inflammatory disorders. The present study was performed to examine whether IL-10 plasmid DNA could suppress development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice, as an initial step towards the development of an appliance for use in dogs with AD. Intradermal injection of IL-10 plasmid DNA markedly inhibited the development of AD-like skin lesions, as evidenced by a marked decrease in skin symptoms and reduced inflammation within the skin lesions. Efficacy was confirmed by significant decreases in eosinophil ratio and serum IgE concentration, and a reduction in the number of Staphylococcus aureus recovered from the ear. Moreover, relative mRNA expression levels of IL-4 and interferon-γ in the skin lesions of mice injected with IL-10 plasmid DNA were also decreased compared with those of control mice. Of note, higher serum IL-10 levels in mice injected with IL-10 plasmid DNA were maintained compared with those in control mice. Taken together, the results indicate that IL-10 plasmid DNA can suppress the development of AD-like skin lesions by suppressing both Th1 and Th2 cell responses. Beneficial effects of IL-10 plasmid DNA may be expected in dogs with AD.

Background: Flowable hemostatic agents may be more advantageous than nonflowable hemostats, as they have capability to cover irregular wound surfaces, fill deep lesions, and easily remove excess materials with irrigation. In this study, we evaluated the hemostatic efficacy of the collagen hemostatic matrix (CHM) compared to FloSeal ® via incisions in the heart and cardiac vessels in a porcine model. Methods:In each of the two female pigs, a total of two incisions were made in seven locations: right atrium (RA), right ventricle (RV), and cardiac vessels, such as the innominate vein (IV), superior vena cava (SVC), pulmonary artery (PA), coronary artery (CA), and aorta. Hemostatic agents were applied directly to the bleeding wounds. In certain location, one incision was treated with the CHM and the other with FloSeal ® , and the time to hemostasis and the degree of bleeding of the two agents were assessed and compared. One week after surgery, the animals were sacrificed, and specimens were collected for histologic evaluation.Results: Bleeding from the vessels with relatively low pressure (the IV, SVC, and RA) was controlled within 1-2 minutes using both a CHM and FloSeal ® . Bleeding from the vessels with high blood pressure (the RV, PA, CA, and aorta) was controlled within 3-10 minutes with the CHM. However, hemostasis in the PA and CA was not achieved with FloSeal ® . Histological analysis revealed that the use of both the CHM and FloSeal ® resulted in foreign body reactions of similar severity. Conclusions:The hemostatic effect and safety of the CHM may be similar to that of FloSeal ® . Further clinical studies must be conducted to validate our results.

ObjectiveEsterified collagen (EC) can be functionalized with heparin to enhance islet graft stability. Growth factors secreted by human adipose-derived stem cells (hADSCs) can bind efficiently to EC-heparin (EC-Hep), which enhances revascularization and cell protection. We investigated the therapeutic potential of a combined heparin-esterified collagen-hADSC (HCA)-islet sheet to enhance islet engraftment.Research design and methodsThis study was designed to assess the efficiency of using EC-Hep as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. After the hADSC-cocultured islets were seeded in the EC-Hep scaffold, islet function was measured by glucose-stimulated insulin secretion test and growth factors in the culture supernatants were detected by protein array. Islet transplantation was performed in mice, and graft function and survival were monitored by measuring the blood glucose levels. β-Cell mass and vascular densities were assessed by immunohistochemistry.ResultsThe EC-Hep composite allowed sustained release of growth factors. Secretion of growth factors and islet functionality in the HCA-islet sheet were significantly increased compared with the control groups of islets alone or combined with native collagen. In vivo, stable long-term glucose control by the graft was achieved after subcutaneous transplantation of HCA-islet sheet due to enhanced capillary network formation around the sheet.ConclusionsThe findings indicate the potential of the HCA-islet sheet to enhance islet revascularization and engraftment in a hADSC dose-dependent manner, following clinical islet transplantation for the treatment of diabetes mellitus.