548 research outputs found

    A standardized procedure to obtain mesenchymal stem/stromal cells from minimally manipulated dental pulp and Wharton’s jelly samples

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    Transplantation of mesenchymal stem/stromal cells (MSCs) has emerged as an effective method to treat diseased or damaged organs and tissues, and hundreds of clinical trials using MSCs are currently under way to demonstrate the validity of such a therapeutic approach. However, most MSCs used for clinical trials are prepared in research laboratories with insufficient manufacturing quality control.In particular, laboratories lack standardized procedures for in vitro isolation of MSCs from tissue samples, resulting in heterogeneous populations of cells and variable experimental and clinical results. MSCs are now referred to as Human Cellular Tissue-based Products or Advanced Therapy Medicinal Products, and guidelines from the American Code of Federal Regulation of the Food and Drug Administration (21 CFR Part 1271) and from the European Medicines Agency (European Directive 1394/2007) define requirements for appropriate production of these cells. These guidelines, commonly called “Good Manufacturing Practices” (GMP), include recommendations about laboratory cell culture procedures to ensure optimal reproducibility, efficacy and safety of the final medicinal product. In particular, the Food and Drug Administration divides ex vivo cultured cells into “minimally” and “more than minimally” manipulated samples, in function of the use or not of procedures “that might alter the biological features of the cells”. Today, minimal manipulation conditions have not been defined for the collection and isolation of MSCs (Torre et al. 2015)(Ducret et al. 2015).Most if not all culture protocols that have been reported so far are unsatisfactory, because of the use of xeno- or allogeneic cell culture media, enzymatic treatment and long-term cell amplification that are known to alter the quality of MSCs. The aim of this study was to describe a standardized procedure for recovering MSCs with minimal handling from two promising sources, the dental pulp (DP) and the Wharton’s jelly (WJ) of the umbilical cord. The quality and homogeneity of the expanded cell populations were assessed by using flow cytometry with criteria that go beyond the International Society of Cellular Therapy (ISCT) guidelines for MSC characterization

    Influence of pristine graphene particle sizes on physicochemical, microstructural and mechanical properties of Portland cement mortars

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    This paper aims to study the effect of the size of pristine graphene (PRG) particles on the compressive and tensile strengths of cement-based mortars and to gain better understandings of the mechanism behind the enhancement of these properties. PRG industrially manufactured by the electrochemical process with a variety of particle sizes including 5 ”m, 43 ”m, 56 ”m, and 73 ”m was used at the optimal dosage of 0.07% by weight of cement binder. The results indicate that mechanical strengths of cement mortars at 7 and 28 days considerably depend on the size of PRG. The mixes with size 56 ”m and 73 ”m show significant influence on both compressive and tensile strengths of cement mortars, which increase approximately 34.3% and 30.1% at 28-day compressive strengths, and 26.9% and 38.6% at 28-day tensile strengths, respectively. On the other hand, the mix with size 43 ”m of PRG addition exhibits a significant increase only in tensile strength, and there are no significant effects on either compressive strengths or tensile strengths of the mix containing 5 ”m particles. The observed enhancement in the mechanical properties of cement mortars by large PRG sizes is attributed to the improvement of cement hydration level, the reduction of cement particles’ distance in cement gels because of the effect of van der Waals forces between PRG sheets, and the mechanical adhesion forces between PRG sheets and cement gels. The results from this study indicate that PRG is not only a promising additive in practical application for building materials to improve the current drawbacks of cement composites, but also a feasible option to support the reduction of cement mass used in cement composites, which could reduce the CO₂ footprint and amount of CO₂ emission into the atmosphere.Van Dac Ho, Ching-Tai Ng, Togay Ozbakkaloglu, Andy Goodwin, Craig McGuckin, Ramesh U. Karunagaran, Dusan Losi

    The Role of the Mucus Barrier in Digestion

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    Mucus forms a protective layer across a variety of epithelial surfaces. In the gastrointestinal (GI) tract, the barrier has to permit the uptake of nutrients, while excluding potential hazards, such as pathogenic bacteria. In this short review article, we look at recent literature on the structure, location, and properties of the mammalian intestinal secreted mucins and the mucus layer they form over a wide range of length scales. In particular, we look at the structure of the gel-forming glycoprotein MUC2, the primary intestinal secreted mucin, and the influence this has on the properties of the mucus layer. We show that, even at the level of the protein backbone, MUC2 is highly heterogeneous and that this is reflected in the networks it forms. It is evident that a combination of charge and pore size determines what can diffuse through the layer to the underlying gut epithelium. This information is important for the targeted delivery of bioactive molecules, including nutrients and pharmaceuticals, and for understanding how GI health is maintained

    Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?

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    There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients
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