Publications (11) View all
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Article: M cell specific markers in man and domestic animals: Valuable tools in vaccine development.
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ABSTRACT: M cells play a pivotal role in the induction of immune responses within the mucosa-associated lymphoid tissues. As such, they are frequently studied for the development of mucosal vaccines. Unfortunately, the lack of a universal M cell marker hampers the progress in this field since researchers need species- and tissue-specific markers in order to isolate, identify or target M cells. Depicting the most appropriate M cell marker for the species and tissue under investigation might, however, be complicated by the numerous publications on this topic, often mentioning both positive and negative results for the tested marker. Therefore, this review gives an overview of the specific M cell markers in man and various domestic and laboratory animals. In addition, current state-of-the-art as regards the use of M cell models and markers in mucosal vaccine development is discussed.Comparative immunology, microbiology and infectious diseases 04/2013; · 2.99 Impact Factor -
Article: Cell type-associated differences in migration, survival and immunogenicity following grafting in CNS tissue.
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ABSTRACT: Cell transplantation has been suggested to display several neuro-protective and/or - regenerative effects in animal models of central nervous system (CNS) trauma. However, while most studies report on clinical observations, currently little is known regarding the actual fate of the cell populations grafted and whether or how the brain's innate immune system, mainly directed by activated microglia and astrocytes, interacts with autologous cellular implants. In this study, we grafted well-characterised neural stem cell, mouse embryonic fibroblast, dendritic cell, bone marrow mononuclear cell and splenocyte populations, all isolated or cultured from C57BL/6-eGFP transgenic mice, below the capsula externa (CE) of healthy C57BL/6 mice and below the inflamed/demyelinated CE of cuprizone-treated C57BL/6 mice. Two weeks post-grafting, an extensive quantitative multicolour histological analysis was performed in order: (i) to quantify cell graft localisation, migration, survival and toxicity, and (ii) to characterize endogenous CNS immune responses against the different cell grafts. Obtained results indicate dependent on the cell type grafted: (i) a different degree of cell graft migration, survival and toxicity, and (ii) a different organisation of the endogenous immune response. Based on these observations, we warrant that further research should be undertaken to understand - and eventually control - cell graft induced tissue damage and activation of the brain's innate immune system. The latter will be inevitable before cell grafting in the CNS can be performed safely and successfully in clinical settings.Cell Transplantation 04/2012; · 5.13 Impact Factor -
Article: Recognition of cellular implants by the brain's innate immune system.
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ABSTRACT: Currently, much attention is given to the development of cellular therapies for treatment of central nervous system (CNS) injuries. Diverse cell implantation strategies, either to directly replace damaged neural tissue or to create a neuroregenerative environment, are proposed to restore impaired brain function. However, because of the complexity of the CNS, it is now becoming clear that the contribution of cell implantation into the brain will mainly act in a supportive manner. In addition, given the time dependence of neural development during embryonic and post-natal life, cellular implants, either self or non-self, will most likely have to interact for a sustained period of time with both healthy and injured neural tissue. The latter also implies potential recognition of cellular implants by the innate immune system of the brain. In this review, we will emphasize on preclinical observations in rodents, regarding the recognition and immunogenicity of autologous, allogeneic and xenogeneic cellular implants in the CNS of immune-competent hosts. Taken together, we here suggest that a profound study of the interaction between cellular grafts and the brain's innate immune system will be inevitable before clinical cell transplantation in the CNS can be performed successfully.Immunology and Cell Biology 11/2010; 89(4):511-6. · 3.66 Impact Factor -
Article: Osteopontin alters the functional profile of porcine microglia in vitro.
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ABSTRACT: Osteopontin is a secreted glycoprotein that is predominantly expressed in bone matrix and kidney tissue. More recently, a neuroprotective role has been attributed to this cytokine since it can be upregulated by microglia in neurodegeneration and inflammation. Our data demonstrate the in vitro expression of osteopontin within primary cultured microglia. Microglia incubated in vitro with different concentrations (0.1 fM - 1 nM) of recombinant osteopontin showed increased proliferation at low concentration (10 fM). Moreover, the conditioned medium of LLC-PK1 cells, a pig renal epithelial cell line and a known source of secreted osteopontin, more than doubled the proliferation of microglia. The addition of an anti-osteopontin polyclonal antibody completely reversed this effect. In addition, treatment with osteopontin dose-dependently inhibited microglial superoxide production. In contrast, the phagocytosis of fluorescent labeled beads was enhanced by osteopontin. In conclusion, osteopontin shifts microglia, at least in vitro, to an alternative functional profile more fit to the immune-balanced microenvironment of the central nervous system.Cell Biology International 09/2012; · 1.48 Impact Factor -
Article: Clinical potential of intravenous neural stem cell delivery for treatment of neuroinflammatory disease in mice?
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ABSTRACT: While neural stem cells (NSCs) are widely expected to become a therapeutic agent for treatment of severe injuries to the central nervous system (CNS), currently there are only few detailed preclinical studies linking cell fate with experimental outcome. In this study, we aimed to validate whether IV administration of allogeneic NSC can improve experimental autoimmune encephalomyelitis (EAE), a well-established animal model for human multiple sclerosis (MS). For this, we cultured adherently growing luciferase-expressing NSCs (NSC-Luc), which displayed a uniform morphology and expression profile of membrane and intracellular markers, and which displayed an in vitro differentiation potential into neurons and astrocytes. Following labeling with green fluorescent micron-sized iron oxide particles (f-MPIO-labeled NSC-Luc) or lentiviral transduction with the enhanced green fluorescent protein (eGFP) reporter gene (NSC-Luc/eGFP), cell implantation experiments demonstrated the intrinsic survival capacity of adherently cultured NSC in the CNS of syngeneic mice, as analyzed by real-time bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and histological analysis. Next, EAE was induced in C57BL/6 mice followed by IV administration of NSC-Luc/eGFP at day 7 postinduction with or without daily immunosuppressive therapy (cyclosporine A, CsA). During a follow-up period of 20 days, the observed clinical benefit could be attributed solely to CsA treatment. In addition, histological analysis demonstrated the absence of NSC-Luc/eGFP at sites of neuroinflammation. In order to investigate the absence of therapeutic potential, BLI biodistribution analysis of IV-administered NSC-Luc/eGFP revealed cell retention in lung capillaries as soon as 1-min postinjection, resulting in massive inflammation and apoptosis in lung tissue. In summary, we conclude that IV administration of NSCs currently has limited or no therapeutic potential for neuroinflammatory disease in mice, and presumably also for human MS. However, given the fact that grafted NSCs have an intrinsic survival capacity in the CNS, their therapeutic exploitation should be further investigated, and-in contrast to several other reports-will most likely be highly complex.Cell Transplantation 11/2010; 20(6):851-69. · 5.13 Impact Factor
