Etanercept therapy in patients with psoriasis and concomitant HCV infection

Treatment of patients with psoriasis and/or psoriatic arthritis and concomitant hepatitis C infection remains difficult. Except for cyclosporine, other drugs have proved unacceptable because of hepatotoxicity in patients with HCV. With the advent of anti-TNF-alpha drugs, including etanercept, new therapeutic options have become available. Our study population was five patients with psoriasis and/or psoriatic arthritis and concomitant chronic HCV infection undergoing etanercept therapy. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viral load were used as markers for liver damage and disease progression, respectively. The Psoriasis Area Severity Index (PASI) was used as a reference parameter for evaluating the therapeutic efficacy of etanercept therapy in improving the clinical skin picture. AST, ALT, viral load and PASI were monitored at 3-month intervals starting from the beginning of therapy up to two years after initiation of etanercept therapy. In four out of five patients, liver enzyme levels and viral load remained substantially unchanged during the course of therapy. In the one remaining patient, viral load and liver enzyme levels increased during etanercept therapy, and then decreased following the initiation of Peg-IFN/ribavirin in combination with anti-TNF-alpha therapy. PASI scores decreased in all five patients. Our data suggest that etanercept therapy is safe and provides an efficacious therapeutic alternative in patients with psoriasis and concomitant HCV infection

Adipose-derived stem cells could sense the nano-scale cues as myogenic-differentiating factors

Microenvironmental cues, such as surface topography and substrate stiffness, may affect stem cells adhesion, morphology, alignment, proliferation and differentiation. Adipose derived stem cells (ASCs) have attracted considerable interest in regenerative medicine due to their easy isolation, extensive in vitro expandability and ability to differentiate along a number of different tissue-specific lineages. The aim of this work was to investigate ASCs adhesion, alignment and differentiation into myogenic lineage on nanofibrous polymeric scaffolds with anisotropic topography. Nanostructured scaffolds with randomized or parallel fibers were fabricated by electrospinning using polycaprolactone (PCL) and the polycarbonate-urethane ChronoFlex AL 80A (CFAL). Cells expressed myosin (fast skeletal) and tropomyosin in all surface topographies 7 days after seeding but myotube formation was only observed on CFAL scaffolds and only few myotubes were formed on PCL scaffolds. The different cell behavior could be ascribed to two main parameters: fibers dimensions and fibers orientation of the substrates that could result in a better myotube formation on CFAL scaffolds

Biodegradable microgrooved polymeric surfaces obtained by photolithography for skeletal muscle cell orientation and myotube development

During tissue formation, skeletal muscle precursor cells fuse together to form multinucleated myotubes. To understand this mechanism, in vitro systems promoting cell alignment need to be developed; for this purpose, micrometer-scale features obtained on substrate surfaces by photolithography can be used to control and affect cell behaviour. This work was aimed at investigating how differently microgrooved polymeric surfaces can affect myoblast alignment, fusion and myotube formation in vitro. Microgrooved polymeric films were obtained by solvent casting of a biodegradable poly-L-lactide/trimethylene carbonate copolymer (PLLA-TMC) onto microgrooved silicon wafers with different groove widths (5, 10, 25, 50, 100 mu m) and depths (0.5, 1, 2.5, 5 mu m), obtained by a standard photolithographic technique. The surface topography of wafers and films was evaluated by scanning electron microscopy. Cell assays were performed using C2C12 cells and myotube formation was analysed by immunofluorescence assays. Cell alignment and circularity were also evaluated using ImageJ software. The obtained results confirm the ability of microgrooved surfaces to influence myotube formation and alignment; in addition, they represent a novel further improvement to the comprehension of best features to be used. The most encouraging results were observed in the case of microstructured PLLA-TMC films with grooves of 2.5 and 1 mu m depth, presenting, in particular, a groove width of 50 and 25 mu m

Microcontact printing of fibronectin on a biodegradable polymeric surface for skeletal muscle cell orientation

BACKGROUND AND OBJECTIVES:</b> Micropatterning and microfabrication techniques have been widely used to control cell adhesion and proliferation along a preferential direction according to contact guidance theory. One of these techniques is microcontact printing, a soft lithographic technique based on the transfer of a "molecular ink" from an elastomeric stamp to a surface. This method allows the useful attachment of biomolecules in a few seconds on a variety of surfaces with sub-micrometer resolution and control, without modifying the biomolecule properties. The aim of this study is to develop an easy and versatile technique for in vitro production of arrays of skeletal muscle myofibers using microcontact printing technique on biodegradable substrata. METHODS: Microcontact printing of fibronectin stripes (10, 25, 50 μm in width) was performed onto biodegradable L-lactide/trimethylene carbonate copolymer (PLLA-TMC) films. C2C12, a murine myoblast cell line, was used for the production of parallel myofibers. RESULTS: This approach proved to be simple, reliable and effective in obtaining a stable pattern of fibronectin on the PLLA-TMC surface as observed by fluorescence microscopy. C2C12 cells were well aligned along the pattern 24 hours after seeding, especially on fibronectin stripes 10 and 25 μm in width. Seven days after confluence cells fused and formed aligned multinucleated cells expressing a-actinin. CONCLUSIONS: Fibronectin patterning seems to be a useful method to induce cell alignment and to improve myotube formation. Further studies will be focused on the possibility of applying external stimuli to these structures to obtain healthy myotubes and to induce myofiber development