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    • "For example, human ES cells maintained using mouse embryonic fibroblasts and/or animal-derived serum replacements were shown to incorporate an immunogenic nonhuman sialic acid (Neu5Gc) capable of inducing an immune response in vitro [56]. Although other studies questioned the extent of Neu5Gc contamination in human ES cell cultures and its immunogenic potential [57-59], significant efforts continue to be made to enable animal product-free culture of human pluripotent cells and their derivatives. As mentioned above, this has led to the development of a variety of animal product replacements including human feeder cells [15], defined media [7], and chemical or recombinant extra-cellular matrices [17]. "
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    ABSTRACT: The first derivation of human embryonic stem cells brought with it a clear understanding that animal models of human disease might be replaced by an unlimited supply of human cells for research, drug discovery, and drug development. With the advent of clinical trials using human pluripotent stem cell-based therapies, it is both timely and relevant to reflect on factors that will facilitate future translation of this technology. Human pluripotent cells are increasingly being used to investigate the molecular mechanisms that underpin normal and pathological human development. Their differentiated progeny are also being used to identify novel pharmaceuticals, to screen for toxic effects of known chemicals, and to investigate cell or tissue transplantation strategies. The intrinsic assumption of these research efforts is that the information gained from these studies will be more accurate, and therefore of greater relevance, than traditional investigations based on animal models of human disease and injury. This review will therefore evaluate how animals and animal-derived products are used for human pluripotent stem cell research, and will indicate how efforts to further reduce or remove animals and animal products from this research will increase the clinical translation of human pluripotent stem cell technologies through drug discovery, toxicology screening, and cell replacement therapies.
    Preview · Article · Mar 2013 · Stem Cell Research & Therapy
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    ABSTRACT: Arterial hypertension is a risk factor for atherosclerosis of whose pathogenesis is unknown. Growing evidence underscores the causative role of endothelial dysfunction. A possible association between Helicobacter pylori infection and cardiovascular and autoimmune disorders has been found. The release of cytotoxic substances either of bacterial origin or produced by the host may represent mediators of these systemic sequelae. The aim of our study was to determine the prevalence of H. pylori infection in hypertensive patients and the effects of H. pylori eradication on blood pressure and on digestive symptoms. Seventy-two hypertensive patients (34 male and 38 female; mean age 53 +/- 12 years) and 70 normotensive controls (35 male and 35 female; mean age 52 +/- 10 years) were enrolled. All patients were subjected to a first ambulatory blood pressure monitoring (ABPM) at enrollment, a 13C urea breath test and a test for IgG-CagA antibodies, and completed the validated dyspepsia questionnaire. H. pylori-positive patients were treated with triple therapy (amoxicillin, clarithromycin and ranitidine bismute citrate) for 7 days. Control of eradication was assessed by 13C urea breath test, and all patients underwent a second ABPM 6 months after enrollment. H. pylori infection was 55% in hypertensive patients, with 90% CagA positivity, and 50% in controls, with 60% CagA positivity. At the first ABPM, blood pressure values were similar in H. pylori-positive and -negative individuals; positive patients showed a significant increase in pyrosis and epigastric pain compared to negative patients. H. pylori was eradicated in 80% of patients and in 85% of controls. At the second ABPM, we found a statistically significant decrease in 24-hour mean blood pressure values when compared to the first ABPM only in the eradicated hypertensive group. Our study demonstrated a significant decrease in blood pressure values, in particular in diastolic blood pressure values, after H. pylori eradication in hypertensive patients. A high prevalence of CagA positivity was found. The association between cardiovascular disease and H. pylori infection seems pronounced only in CagA-positive patients. The possible links between hypertensive disease and H. pylori infection may involve the activation of the cytokine cascade with the release of vasoactive substances from the primary site of infection, or molecular mimicry between the CagA antigens of H. pylori and some peptides expressed by endothelial cells and smooth muscle cells.
    No preview · Article · Jan 2004 · Helicobacter
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    ABSTRACT: Glycans cover all cellular surfaces and, not surprisingly, are involved in many facets of stem cell biology and technology. For instance, coaxing stem cells to either proliferate or differentiate into the specific cell types needed for transplantation requires intricate glycan-dependent modulation of signalling molecules such as FGF-2, Wnt, and Notch. Moreover, owing to their prominent cell-surface localization and lineage-specific signatures, glycan epitopes such as the stage-specific embryonic antigens (Lewis X/SSEA-1, SSEA3-4) and tumor-rejection antigens (TRA1-60, 1-81) are ideally suited for identifying and isolating specific cell types from heterogeneous populations. Finally, the non-human sialic acid Neu5Gc has been detected on the surface of human embryonic stem cells because of metabolic incorporation from animal products used for their culture. Transplantation of Neu5Gc-contaminated cells poses immunological risks due to the presence, in humans, of circulating antibodies recognizing this glycan epitope.
    Preview · Article · Sep 2007 · Current Opinion in Chemical Biology
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