Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes.

Despite a significant increase in EPCs and release of cytochemokines during CABG, age is a major limiting factor for mobilization of EPCs. Further studies are necessary to improve the strategies for mobilization, ex vivo expansion, and re-transplantation of EPCs in aging patients.

Abstract-We evaluated the healing potential of human fetal aorta-derived CD133ϩ progenitor cells and their conditioned medium (CD133 ϩ CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2ϫ10 4 CD133 ϩ or CD133 Ϫ cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133 ϩ cells expressed high levels of wingless (Wnt) genes, which were downregulated following differentiation into CD133Ϫ cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133ϩ cells accelerated wound closure as compared with CD133Ϫ or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133ϩ cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133ϩ CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by coadministering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133 ϩ CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of Wnt expression. The promigratory and proangiogenic effect of CD133 ϩ CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. Key Words: ischemia Ⅲ wound healing Ⅲ diabetes Ⅲ stem cells Ⅲ angiogenesis C hronic wounds represent a relevant clinical and socioeconomic burden, with diabetic foot ulcers alone causing costs of 300 million pounds per annum to the United Kingdom National Health System. 1 Diabetic patients with foot ulcers associated with peripheral vascular disease manifest the worst outcome, with higher amputation and mortality rates than patients carrying nonischemic ulcers. 2,3 Although the efficacy of a topical gel formulation of recombinant human platelet-derived growth factor-BB was recently demonstrated in patients with nonischemic neuropathic ulcers, 4 most ischemic ulcers are refractory to conventional treatment and growth factor (GF) therapy. 5 Therefore, new strategies for the cure of life-threatening ischemic ulcers are urgently awaited.Preliminary evidence supports the potential of adult or fetal stem/progenitor cells for the healing of skin ulcers. 6 -8 However, because of the lack of an appropriate preclinical model, no information is available regarding the effectiveness of cell therapy on ischemic diabetic foot ulcers. The healing activity of stem cells is credited to their ability to transdifferentiate into the vascular and nonvascular components of injured tissue, as well as to secretion of GFs, which may activate endogenous modulators of angiogenesis in the recipient. 9 -11 Notably, fetal stem cells show significant advantages over their adult counterparts in terms of proliferative capa...

Eukaryotic expression vectors can be delivered to macrophages using attenuated self-destructing Listeria monocytogenes. L. monocytogenes cells are preferentially lysed in the host cell macrophage cytosol by the production of a PactA-dependent Listeria-specific phage lysin. Efficient expression of the cloned reporter genes by the macrophages and subsequent antigen presentation were achieved after the delivery of eukaryotic expression vectors by the attenuated suicide L. monocytogenes strain. After delivery by L. monocytogenes plasmid DNAs were found to integrate into the macrophage cell's genome at a frequency of about 10(-7).