1,721,112 research outputs found
Human mesenchymal stromal cells : biological characterization and clinical application
Get PDFThis thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has been investigated as a potential novel source of MSCs for clinical application and the immunomodulatory properties of UCB-derived MSCs have been characterized in comparison with those of MSCs of bone marrow (BM) origin. Moreover, it has been attempted to optimize the experimental conditions for MSC ex vivo expansion. Alternative culture methods, devoid of animal proteins, have been applied by introducing expansion procedures based on platelet-derived growth factors. The potential susceptibility of MSCs to undergo malignant transformation after long-term in vitro culture has been investigated and discussed in view of their clinical application, especially in immunocompromised hosts. The role of MSC therapy in the context of hematopoietic stem cell transplantation (HSCT) has been explored, focusing in particular on the co-transplantation of MSCs to promote engraftment of hematopoietic progenitors, and on the administration of MSCs for the treatment of steroid-resistant, severe acute graft-versus-host disease (GvHD). The role of MSCs in the treatment of inflammatory bowel diseases refractory to conventional therapies, as well as the concept for treating refractory autoimmune diseases has been discussed.UBL - phd migration 201
Immunomodulatory properties of human multipotent stromal cells
Get PDFThe application of MSC as therapeutic agent to treat a variety of immune related diseases is currently under investigation in preclinical and clinical studies. Although promising results have been reported, more insight in the basic MSC biology and in the mechanisms by which MSC modulate the immune system are necessary to optimize the safe and effective application of MSC in the clinic. This thesis describes our contributions to the understanding of the immunomodulatory mechanisms of MSC. We also investigated some translational aspects of MSC therapy, aiming at selecting the preferred tissue source for clinical application. The work supports the role of MSC as powerful modulators of the innate and adaptive immune response. Immune suppression by MSC through modulation of monocytes and macrophages sheds a new light on the possible mechanism of therapeutic application of MSC for immunomodulatory purposes and the invo lvement of type 2 macrophages in tissue repair might link the immunomodulatory properties of MSC to the possibly advantageous effects of MSC for tissue regeneration. The fundamental studies on the immunomodulatory effects of MSC may provide valuable knowledge on how to proceed with applying MSC as a therapy in immune related diseases.Greiner Bio-one; Becton Dickinson; PeprotechUBL - phd migration 201
Cell therapy in ischemic heart disease models : role of inflammation, paracrine factors and hypercholesterolemia
Get PDFThis thesis focuses on the potential of cell-based therapy in ischemic heart disease and the role of the inflammatory response after myocardial infarction (MI). Chapter 2 reviews the specific myocardial inflammatory events that occur following MI and explores the potential role of cell therapy, in specific of the mesenchymal stromal cell (MSC), to positively influence this process. In chapter 3 we studied the usefulness of a clinically relevant transient ischemia MI model in immunodeficient mice to investigate the potential of human stem cell therapy and compared this to the commonly used animal MI model via permanent ischemia. Next, in chapter 4 we aimed to extend our previous research regarding the positive therapeutic effects of MSC therapy after MI by injecting MSCs stimulated with the pro-inflammatory cytokine interferon-γ, since pro-inflammatory priming has shown additional beneficial effects in several experimental disease models. Chapter 5 evaluates the short-term effect of human cardiomyocyte progenitor cell infusion on cardiac function in an animal MI model. Chapter 6 discusses the effect of diet-induced hypercholesterolemia on both cardiac function and inflammation after myocardial ischemia-reperfusion injury. Finally, chapter 7 provides an overview of the results described in this thesis, and discusses future perspectives.TeRM Smartmix Program Abbott Vascular Servier Nederland Farma B.V. Toshiba Medical Systems Nederland Pfizer B.V. Dr. F.E. Posthumus Meyjesfonds Alrijne Zorggroep Nederlandse HartstichtingUBL - phd migration 201
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Therapeutic immune regulation by mesenchymal stromal cells
No full textStemcel biology/Regenerative medicine (incl. bloodtransfusion
Clinical and laboratory features of mesenchymal stromal cells in pediatric stem cell transplantation
Get PDFThis thesis describes the clinical use and laboratory findings of bone marrow (BM) derived, ex-vivo expanded human Mesenchymal Stromal Cells (MSCs) in pediatric stem cell transplantation. Advances in transplant technologies have permitted the use of __alternative donors__, i.e. haploidentical peripheral blood stem cells and umbilical cord blood, as a source of donor hematopoietic stem cells. MSCs located in the bone marrow form the stromal network, essential for the support of normal hematopoietic stem cell growth and development. Methods to expand MSCs sufficient for clinical uses have recently become available. In vitro experiments show MSCs interact with various cells of both the innate and adaptive immune system, which overall results in the induction of an anti-inflammatory state. The ability of MSCs to support hematopoietic stem cell growth coupled with their potent immune suppressive effects mean that they are ideal candidate cells to explore in the context of overcoming some of the problems specifically associated with the use of alternative donors. In this thesis, we therefore attempted to address the most relevant of these issues that, given the known properties of MSCs, would allow us to assess the possible usefulness of MSCs as an innovative strategy to resolve them.Willem Alexander Kinder en Jeugd Centrum, Pfizer BV, Genzyme Nederland, Amgen BV, Gilead Sciences BVUBL - phd migration 201
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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