RESUMEN
Galectin-3 (Gal-3), a ß-galactoside-binding lectin that is expressed in mammalian cells, is known to modulate several biological functions such as cell-cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The goal of this study was to evaluate the ability of Gal-3 depletion apheresis using an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation induced by Complete Freund's Adjuvant injection in a skin inflammation porcine model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding immuno-affinity column reduces plasma Gal-3 levels to below limits of quantitative detection, and results in significant decrease in skin inflammation, including degree and duration of inflammatory lesions. Human plasma was tested ex vivo and found to be efficiently depleted using the anti-Gal-3 affinity column. This study demonstrates the potential of Gal-3 depletion apheresis as a therapeutic method for inflammation-mediated disease, supporting continued research in this area for clinical application.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Galectina 3/aislamiento & purificación , Inflamación/terapia , Animales , Adyuvante de Freund , Galectina 3/sangre , Humanos , Inflamación/inducido químicamente , Piel/patología , Porcinos , Resultado del TratamientoRESUMEN
BACKGROUND: Deficiency of autologous skin for reconstruction of severe wounds is a major problem in plastic surgery. Autologous substitutes can provide additional coverage, but due to the duration of production, treatment is significantly delayed. The allogeneic approach offers a potential of having an off-the-shelf solution for the immediate application. METHODS: In this study, we assess the engraftment and immunogenicity of allogeneic bilayered bioengineered skin prepared by a self-assembly method. Bioengineered skin has the potential immunological advantage of lacking passenger leukocytes including antigen-presenting cells. The skin constructs were transplanted across major histocompatibility complex (MHC) barriers in a porcine animal model. Animals received a second grafting of the same skin construct 7 weeks after the first set of grafts together with MHC-matched constructs to assess for clinical sensitization. RESULTS: All alloconstructs successfully engrafted with histologic evidence of neovascularization by day 4. Complete cellular rejection and tissue loss occurred by day 8 for most grafts. After the second application, accelerated rejection (<4 days) took place with the development of swine MHC-specific cytotoxic alloantibody. CONCLUSIONS: These data demonstrate preclinically that self-assembled allogeneic constructs engraft and reject similar to allogeneic skin despite the absence of professional donor antigen-presenting cells.
Asunto(s)
Trasplante de Piel , Ingeniería de Tejidos , Animales , Células Presentadoras de Antígenos/inmunología , Rechazo de Injerto , Isoanticuerpos/biosíntesis , Piel , Trasplante de Piel/efectos adversos , Porcinos , Porcinos Enanos , Trasplante HomólogoRESUMEN
OBJECTIVES: Design and construct a tooth-brushing simulator incorporating control of brushing variables including brushing force, speed and temperature, thereby facilitating greater understanding of their importance in toothpaste abrasion testing methodologies. METHODS: A thermostable orbital shaker was selected as a base unit and 16- and 24-specimen brushing rigs were constructed to fit inside, consisting of: a square bath partitioned horizontally to provide brushing channels, specimen holders for 25 mm diameter mounted specimens to fit the brushing channels and individually weighted brushing arms, able to support four toothbrush holders suspended over the brushing channels. Brush head holders consisted of individually weighted blocks of Delrin, or PTFE onto which toothbrush heads were fixed. Investigating effects of key design criteria involved measuring abrasion depths of polished human enamel and dentine. RESULTS: The brushing simulator demonstrated good reproducibility of abrasion on enamel and dentine across consecutive brushing procedures. Varying brushing parameters had a significant impact on wear results: increased brushing force demonstrated a trend towards increased wear, with increased reproducibility for greater abrasion levels, highlighting the importance of achieving sufficient wear to optimise accuracy; increasing brushing temperature demonstrated increased enamel abrasion for silica and calcium carbonate systems, which may be related to slurry viscosities and particle suspension; varying brushing speed showed a small effect on abrasion of enamel at lower brushing speed, which may indicate the importance of maintenance of the abrasive in suspension. CONCLUSIONS: Adjusting key brushing variables significantly affected wear behaviour. The brushing simulator design provides a valuable model system for in vitro assessment of toothpaste abrasivity and the influence of variables in a controlled manner. Control of these variables will allow more reproducible study of in vitro tooth wear processes.