Biodegradable scaffolds--delivery systems for cell therapies

The use of cells as therapies for disease, repair and regeneration of tissues is one of the new challenges in modern therapeutics. To facilitate the ability to localise, condition and protect cells, biodegradable scaffolds are being developed that will improve the efficiency of these treatments. Thus, cell delivery systems, either scaffolds or capsules, play a pivotal role in the success of these techniques. This review discusses these novel approaches. The selection of scaffold materials is addressed alongside issues of biocompatibility. The current research developments in smart scaffolds, which focus on the formation of biomimetic scaffolds, new fabrication techniques capable of controlling architecture and microstructure of scaffolds, and the production of injectable and in situ crosslinked scaffolds, are outlined. Finally, the continuing challenges that will drive future research in the cell therapies are highlighted.     

Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice

Atherosclerosis results from accumulation of macrophages and extracellular matrix in the arterial wall. Decorin, a small matrix proteoglycan, is able to regulate cell proliferation, migration and growth factors' activity. We investigated the effect of decorin overexpression on atherosclerosis progression in apolipoprotein E-deficient (ApoE(-/-)) mice. Female ApoE(-/-) mice, 10 weeks old (early treatment, n = 20) and 20 weeks old (delayed treatment, n = 20) were administered intravenously with either an adenovirus (2.5 x 10(9) plaque-forming units/mouse) containing human decorin gene (Ad-Dcn) or beta-galactosidase (LacZ), or PBS. Transgenic decorin was mainly expressed in the liver, and was secreted in the plasma up to 4 weeks. Six weeks after treatment, no significant difference in aortic root lesion size was observed between LacZ- and PBS-control groups. In contrast, Ad-Dcn-treated mice showed significantly reduced atherosclerotic lesions as compared to controls in both early and delayed treatment groups (2.9 +/- 1.1% versus 5.5 +/- 0.4%; p = 0.004 and 13.4 +/- 1.3% versus 19.9 +/- 1.41%; p = 0.009, respectively). In parallel, macrophage, gelatinase activity and collagen plaque content were also reduced. Interestingly, plasma triglycerides were reduced and decorin formed complexes with transforming growth factor-beta1 (TGF-beta1) that resulted in reduced circulating free-TGF-beta1. In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE(-/-) mice resulting in slowing down of disease progression.     

Nicotine inhibits firing activity of dorsal raphe 5-HT neurones in vivo

It is established that the brain monoaminergic systems are among the main targets of several dependence-inducing drugs, including nicotine. In the present study extracellular electrophysiological recordings were performed to investigate the effects of nicotine on dorsal raphe 5-HT neurones. Nicotine, administered systemically (50-400 microg/kg, i.v.) in chloral hydrate-anaesthetised rats, induced a transient inhibition of the majority of 5-HT neurones recorded (38 of 45). The inhibition was rapid in onset (about 30 s) and the firing rate returned to baseline within 1-3 min. No apparent tachyphylaxis was observed to this inhibitory effect. The centrally acting nicotine antagonist mecamylamine (4 mg/kg, i.v.), but not the peripherally acting nicotine antagonist chlorisondamine (0.3 mg/kg, i.v.) antagonised the nicotine-induced inhibition of 5-HT neurones. The inhibition of 5-HT neurones was also blocked with a selective 5-HT1A receptor antagonist (WAY 100635; 0.1 mg/kg, i.v.), indicating a possible involvement of somato-dendritic 5-HT1A receptors in the effect of nicotine. Interestingly, microiontophoretic application of nicotine into the dorsal raphe failed to inhibit 5-HT neurones, suggesting an indirect effect of nicotine on 5-HT neurones, possibly involving afferent pathways.