Comparison of ex vivo expansion culture conditions of mesenchymal stem cells for human cell therapy

Mesenchymal stem cells (MSCs) are multipotent stem cells. Based on their properties, several clinical trials have been designed to explore their potential therapeutic effect. Fetal calf serum (FCS, commonly used for in vitro expansion) is an undesirable source of xenogeneic antigens and bears the risk of transmitting contaminations. As an alternative for FCS, platelet lysate (PL) and both autologous and allogeneic human serum have been proposed. The aim of this study is to compare the culture of bone marrow (BM)- derived MSCs in the presence of different serum supplements to determine the effect on cell growth, differentiation potential, and immunologic function

Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

Background: Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke. Methods: BALB/Ca-RAG2-/-gc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM. Results: In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation. Conclusions: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2-/- gC -/- allows cell transplant from different species, even human, to be analyzed

Knowledge and Beliefs about Mechanism of Action of Birth Control Methods among European Women

Background: Adequate knowledge is essential for making informed decisions. We attempted to determine the level of knowledge about mechanisms of action of birth control methods in five representative samples of European women. Study design: Randomly selected women, aged 18-49 years, completed an anonymous survey in Germany, France, the UK, Sweden and Romania (N=1137). Participants were asked about how contraceptive methods work and if providers should inform them about this issue. Multiple linear regression was used to evaluate women’s characteristics associated with their knowledge of mechanisms of action. Results: The majority of women identified the unequivocal mode of action of condoms, sterilization and abortion. Less than 2% identified all possible mechanisms of action of hormonal contraceptives and intrauterine devices. Highly-educated women correctly identified the mechanism or mechanisms of action of more methods than less educated women (β coef.=0.22, 95%CI=0.01-0.43). Regardless of their sociodemographic characteristics and their belief about when human life begins, most women (75%) stated that the provider should inform them about possible postfertilization effects. Conclusions: European women have low knowledge about mechanisms of action of several contraceptive methods. The majority want to be informed about possible postfertilization effects. Since adequate knowledge is essential for making informed decisions, providers are encouraged to inform women about all possible mechanisms of action of contraceptives

Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice

The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasio

Intelligent image-based colourimetric tests using machine learning framework for lateral flow assays

This paper aims to deliberately examine the scope of an intelligent colourimetric test that fulfils ASSURED criteria (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable) and demonstrate the claim as well. This paper presents an investigation into an intelligent image-based system to perform automatic paper-based colourimetric tests in real-time to provide a proof-of-concept for a dry-chemical based or microfluidic, stable and semi-quantitative assay using a larger dataset with diverse conditions. The universal pH indicator papers were utilised as a case study. Unlike the works done in the literature, this work performs multiclass colourimetric tests using histogram based image processing and machine learning algorithm without any user intervention. The proposed image processing framework is based on colour channel separation, global thresholding, morphological operation and object detection. We have also deployed a server based convolutional neural network framework for image classification using inductive transfer learning on a mobile platform. The results obtained by both traditional machine learning and pre-trained model-based deep learning were critically analysed with the set evaluation criteria (ASSURED criteria). The features were optimised using univariate analysis and exploratory data analysis to improve the performance. The image processing algorithm showed >98% accuracy while the classification accuracy by Least Squares Support Vector Machine (LS- SVM) was 100%. On the other hand, the deep learning technique provided >86% accuracy, which could be further improved with a large amount of data. The k-fold cross validated LS- SVM based final system, examined on different datasets, confirmed the robustness and reliability of the presented approach, which was further validated using statistical analysis. The understaffed and resource limited healthcare system can benefit from such an easy-to-use technology to support remote aid workers, assist in elderly care and promote personalised healthcare by eliminating the subjectivity of interpretation

A new valuation school : Integrating diverse values of nature in resource and land use decisions

We are increasingly confronted with severe social and economic impacts of environmental degradation all over the world. From a valuation perspective, environmental problems and conflicts originate from trade-offs between values. The urgency and importance to integrate nature's diverse values in decisions and actions stand out more than ever. Valuation, in its broad sense of 'assigning importance', is inherently part of most decisions on natural resource and land use. Scholars from different traditions -while moving from heuristic interdisciplinary debate to applied transdisciplinary science- now acknowledge the need for combining multiple disciplines and methods to represent the diverse set of values of nature. This growing group of scientists and practitioners share the ambition to explore how combinations of ecological, socio-cultural and economic valuation tools can support real-life resource and land use decision-making. The current sustainability challenges and the ineffectiveness of single-value approaches to offer relief demonstrate that continuing along a single path is no option. We advocate for the adherence of a plural valuation culture and its establishment as a common practice, by contesting and complementing ineffective and discriminatory single-value approaches. In policy and decision contexts with a willingness to improve sustainability, integrated valuation approaches can be blended in existing processes, whereas in contexts of power asymmetries or environmental conflicts, integrated valuation can promote the inclusion of diverse values through action research and support the struggle for social and environmental justice. The special issue and this editorial synthesis paper bring together lessons from pioneer case studies and research papers, synthesizing main challenges and setting out priorities for the years to come for the field of integrated valuation.Peer reviewe

Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice

Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) γC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 × 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok

O pensar vivenciado na formação de professores

Analisa-se, neste artigo, um estudo de caso que discute a possibilidade de desenvolvimento do pensar vivenciado na formação de professores. A formação de professores é correntemente conduzida a partir de uma visão reducionista intelectual. Neste estudo, a formação de professores é entendida dentro de uma visão ampliada que inclui o desenvolvimento de forma integrada do querer, sentir e pensar. Ancorados em trabalhos anteriores de Goethe, Schiller e Rudolf Steiner, destacamos a importância e o impacto do trabalho com ciência, atividades criativo-artísticas e desenvolvimento pessoal no processo de formação de professores