817 research outputs found
Mesenchymal stromal cells and hematopoietic stem cell transplantation
Stemcel biology/Regenerative medicine (incl. bloodtransfusion
Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation
In addition to their stem/progenitor properties, mesenchymal stromal cells (MSCs) possess broad immunoregulatory properties that are being investigated for potential clinical application in treating immune-based disorders. An informed view of the scope of this clinical potential will require a clear understanding of the dynamic interplay between MSCs and the innate and adaptive immune systems. In this Review, we outline current insights into the ways in which MSCs sense and control inflammation, highlighting the central role of macrophage polarization. We also draw attention to functional differences seen between vivo and in vitro contexts and between species. Finally, we discuss progress toward clinical application of MSCs, focusing on GvHD as a case study
Human mesenchymal stromal cells : biological characterization and clinical application
This 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
The 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
This 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
W.E. Sangster: Sermons in America
Listened to by huge congregations in Britain, and perhaps the most recognizable British Methodist voice in the mid-twentieth century, W.E. Sangster was, in anyone's estimation, a giant of Methodism. This volume captures the preaching of Sangster in his prime, on the occasion of the 1956 World Methodist Conference in Junaluska, North Carolina. The research for this volume brings into the public domain ten sermons, nine previously unpublished, being transcripts of rare and damaged recordings, meticulously transcribed and annotated by the author on the subject of holy living, one of Methodism's characteristic theological emphases
Letter from Dr. W.E. Green to Mr. V. [John Victor] Carson, October 18, 1943
Seeking land in the area of Redondo Beach or Inglewood
Therapeutic immune regulation by mesenchymal stromal cells
Stemcel biology/Regenerative medicine (incl. bloodtransfusion
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