Dissertations / Theses on the topic 'Cellules CD34+hématopoïétiques'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 38 dissertations / theses for your research on the topic 'Cellules CD34+hématopoïétiques.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
Saeland, Sem. "Caractérisation et physiologie in vitro des cellules hématopoïétiques humaines exprimant l'antigène CD34." Lyon 1, 1992. http://www.theses.fr/1992LYO1H053.
Li, Na. "Expansion des cellules souches hématopoïétiques dans les systèmes de cocultures des cellules endothéliales et des cellules stromales." Nancy 1, 2005. http://www.theses.fr/2005NAN11320.
Croisille, Laure. "Caractérisation d'une population de progéniteurs hématopoïétiques humains primitifs CD34++CD38-, et étude de leur régulation par le microenvironnement médullaire." Paris 7, 1997. http://www.theses.fr/1997PA077350.
Traore, Yves. "Divers aspects de polymorphisme de la molécule CD34 : antigène des cellules souches hématopoïétiques humaines." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX22010.
Zebian, Abir. "Etude du facteur de réparation de l’ADN, Xeroderma pigmentosum du groupe C (XPC), dans les cellules souches hématopoïétiques." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0223/document.
DNA damage may accumulate in hematopoietic stem cells (HSC) due to external ormetabolic stresses, leading to perturbation in their function and/or maintenance. Nucleotide excisionrepair (NER), initiated in the DNA by the stop of transcription (TCR) or by the recognition of distortionsin transcribed regions (GGR), is necessary for long-term hematopoiesis. XPC, a key factor in GGR, isimplicated in oxidative stress. The laboratory has demonstrated that XPC loss leads to theaccumulation of mutations, metabolic stress and carcinogenesis. Our objective is to evaluate XPCexpression and its role in HSC maintenance and differentiation. Results showed that XPC is highlyexpressed in immature CD34+ cells compared to mature CD34- cells. In addition, XPC appeared withthree different molecular weights, certainly linked to post-translational modifications. XPC silencing byshRNA did not affect the proliferation or the progenitor ability of CD34+ cells in vitro. However, deficientcells transplanted in immunodeficient mice disappeared progressively, suggesting the loss of HSCs ortheir differentiation capacity. Postulating that mutations accumulate with time, we have studiedhematopoiesis in young and aged XPC deficient mice. Differences described in young and agedhematopoiesis systems were found but, surprisingly, no difference was observed between wild typeand mutant mice at any age or genotoxic stress. Data from human cells demonstrate a potential rolefor XPC in HSC but new investigations are necessary to better understand the mechanisms implicatedand if XPC may participate in leukemogenesis
Aveni-Piney, Maud D'. "Le rôle immunomodulateur dans la réponse allo-immune de cellules hématopoïétiques mobilisées par du G-CSF." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T021.
Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is the most effective immunotherapy for acute leukemia, due to the development of graft-versus-leukemia (GVL) effect mediated by alloreactive donor T cells. However, donor T cells specific for recipient alloantigens are also responsible for graft-versus-host disease (GVHD), a life-threatening complication that frequently occurs after allo-HSCT. The administration of Granulocyte colony stimulating factor (G-CSF) is routinely performed to collect Peripheral Blood Stem Cells (PBSC) from healthy donors for allo-HSCT. Few studies identified that G-CSF can induce myeloid suppressive cells in mice (CD11b+ Gr1+) with no human counterpart. We demonstrated in our study that G-CSF can induce a new population named CD34+Monocyte. The cumulative incidence of acute grade II to IV GVHD following allo-HSCT was lower in patients receiving grafts containing CD34+ monocyte frequencies above 12% of the CD34+ population. In mice, we demonstrated that G-CSF mobilized a highly conserved CD34+ monocyte population. CD34+Monocytes require T cell-mediated IFN-γ to produce Nitric Oxide that inhibits T cell activation and proliferation. In vivo, we report that CD34+ monocyte-derived NO regulates the alloreactive response by inducing T cell apoptosis and subsequently, the induction of regulatory T cells. In fact, uptake of apoptotic T cells by macrophages triggers them to produce high levels of TGF-β that drives the expansion of Tregs and induces immune tolerance. Such tolerogenic monocytes could represent a good candidate for the development of novel immunoregulatory and therapeutic cellular therapies
Golfier, François. "Greffe in utero de cellules souches hématopoïétiques foetales humaines : purification de cellules CD34+/++ de foie foetal et de moëlle osseuse foetale." Lyon 1, 2001. http://www.theses.fr/2001LYO1T007.
Refeyton, Alice. "La survie et les adaptations métaboliques des cellules primitives mésenchymateuses et hématopoïétiques en anoxie et anoxie/aglycémie." Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0028.
Mesenchymal stromal cells (MStroC) comprise multipotent stem cells (SC) capable of regenerating tissues damaged by ischemic insults. However, high mortality of MStroC after transplantation is highlighted during their engraftment. Therefore, exploring strategies to improve the viability of cell grafts constitutes the challenge of cell therapy. To this end, we performed functional and metabolic analyzes on two different types of populations containing somatic SC: MStroC and a population of hematopoietic niche partner cells, CD34+.MStroC or CD34+ cells were cultured under conditions of anoxia (absence of O2) and ischemic type (anoxia/aglycemia, absence of O2 and glucose, AA) or at 3% O2 corresponding to the physiological optimal concentration, then analyzed.Functional assays reveal that MStroC and CD34+ cells exhibit complete proliferation and differentiation properties in anoxia. Functional analyzes of single cells and gene expression revealed that MStroC and CD34+ are not only maintained in an AA state, but are those in which SC, having the highest proliferation and differentiation capacity, are the most enriched. Multiparametric metabolic analysis shows that survival in anoxia is mainly supported by glycolysis and lipid metabolism. On the other hand, the energy homeostasis of MStroC in the AA condition is partially ensured by anaerobic mitochondrial activity particularly involving mitochondrial complexes I, III and ubiquinone. Furthermore, a significant accumulation of succinate in this condition for both types of SC was demonstrated. This is due in part to an inversion of succinate dehydrogenase, which in turn is driven by fumarate spillover from purine nucleotide degradation and malate-aspartate shuttle activity. However, major pathways contributing to succinate accumulation include glycogen-induced glucose/pyruvate stimulation, as well as ketone body, amino acid, and propanoate metabolism which provide succinyl-CoA converted to succinate. Furthermore, MStroC ischemia survival is linked to sulfide metabolism and H2S consumption, as well as improved survival in the presence of H2S donors. SQR-mediated H2S oxidation results in reverse electron transport at mitochondrial complex I, using glutathione as an electron acceptor. The analysis of the use of energy substrates showed that CD34+ cells in anoxia seem to mainly use simple sugars in order to fuel the glycolytic pathway and a consequent reduction in mitochondrial metabolism compared to the 3% O2 condition. In contrast, in AA, Krebs cycle intermediates are used intensively to provide the coenzyme NAD/NADH.Our results reveal a great metabolic flexibility of MStroC and CD34+ populations based on the enrichment of somatic SC detected in anoxia or in the condition mimicking ischemia. Thus, unlike differentiated cells, somatic SC (mesenchymal and hematopoietic) have the capacity to survive in conditions of anoxia and aglycemia using the evolutionary conservative energy pathways existing in early eukaryotes living in anoxic zones enriched in sulfide . Exploiting this ex vivo conditioning under conditions mimicking ischemia could constitute a strategy to improve the survival of MStroC implanted in hypoxic/ischemic tissues
Jobin, Christine. "Expansion ex vivo des cellules CD34+ du sang adulte : étude du microenvironnement et caractérisation des cellules générées en condition d'hypoxie." Master's thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27068.
Moreau, Isabelle. "Étude du rôle des cellules stromales de moelle osseuse humaine dans le soutien de l'hématopoièse in vitro." Lyon 1, 1992. http://www.theses.fr/1993LYO1T001.
Boucher, Jean-François. "Étude des effets de l'hyperthermie légère sur la prolifération et la différenciation des cellules hématopoïétiques CD34+ issues de sang de cordon ombilical." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24987/24987.pdf.
Grafte-Faure, Stéphanie. "Phases précoces de l'hématopoïèse humaine. Effet de l'IL-12 sur les progéniteurs hématopoïétiques primitifs." Rouen, 1999. http://www.theses.fr/1999ROUES085.
Hammoud, Mohammad. "Effet de l’association des basses concentrations d’O2 et des cellules stromales mésenchymateuses sur l’expansion ex vivo des cellules souches et progénitrices hématopoïétiques." Thesis, Besançon, 2012. http://www.theses.fr/2012BESA3008/document.
To optimize at best the hematopoietic engraftment, we suggest in this work to improve the ex vivo expansion conditions by moving them closer to physiology. Indeed, we propose to culture placental CD34+ (HSC/PH) on MSC layer in combination with LO2-C to ensure the amplification of HP together with the maintenance/expansion of HSC. Compared to the single culture and/or atmospheric oxygenation, our experimental model allows a better maintenance of primitive HP (Pre-CFC) and HSC together with a quite good amplification of total cells, CD34+ cells and committed HP despite of lower than control condition. Moreover, exogenous IL-3 shows crucial effect in co-culture at LO2-C (1.5% O2) since its addition better preserves and even increases the number of HSC compared to the CD34+ cells control from D0. We then studied the secretion of soluble factors in culture supernatants and found that IL-6, VEGF and IL-8 were present in larger quantities at LO2-C in both co-culture and MSC culture. Finally, the CD146, CD49a, CD54, CD200 and CD105 membrane antigens appear to be up-regulated in MSCs when incubated at 5% O2. However, the involvement of these factors and antigens in paracrine effect and/or direct cell to cell contact mechanisms at LO2-C requires further investigations. In conclusion, the combination of LO2-C and MSC would be promising in the field of HSC/PH grafts expansion to achieve its main objective of reducing the post-transplant cytopenia period together with maintaining the long-term graft potential
Tounkara, Fatoumata Korika. "Étude des effets de l'hyperthermie légère sur la prolifération et la différenciation des cellules souches hématopoïétiques CD34+ issues du sang de cordon ombilical." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/26949/26949.pdf.
Ravet, Emmanuel. "Le transfert de gènes dans les cellules hématopoïétiques humaines : application à l'étude du rôle du facteur de transcription TAL-1/SCL au cours de l'hématopoïse humaine." Paris 7, 2003. http://www.theses.fr/2003PA077102.
Ame, Thomas Patricia. "Impact de la présence de cellules tumorales au sein de la moëlle osseuse sur les progéniteurs hématopoïetiques médullaires CD34+ au cours des hémopathies lymphoïdes B matures." Besançon, 2004. http://www.theses.fr/2004BESA3015.
Hermitte, Francis. "Rôle des variations des concentrations d'O2 sur la prolifération, le cycle cellulaire et la fonctionnalité des cellules souches hématopoïétiques." Bordeaux 2, 2005. http://www.theses.fr/2005BOR21254.
Hematopoiesis allows the permanent blood cell production from hematopoietic stem cells (HSC), which can be identified by their cell surface expression of the CD34 antigen. Hematopoiesis is regulated by various factors including O2 concentration ranging from 0 to 4 % in the bone marrow (hypoxia). We report here that culture of CD34+ cells at 3 % O2 allows their expansion with a better amplification of HSC. Severe hypoxia (0,1 %) favors the maintenance and return to quiescence of HSC after division. In both cases, cultured HSC engraft immunodeficient mice. The maintenance in quiescence is observed in the normal primitive hematopoietic cell line FDCP-Mix when cultured in hypoxia as well as with cobalt chloride (CoC1 2), a hypoxic mimetic. On the contrary, CoC1 2 induces HeLa cell apoptosis. Actually, we investigate peripheral blood HSC expansion in a medium used in clinic
Peytour, Yann. "Les cellules CD34+ du sang périphérique en condition d’homéostasie : Elution à partir de filtres de leucoréduction : Etude de l’effet des basses concentrations d’oxygène (0,1%) sur la biologie des cellules souches hématopoïétiques." Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21874/document.
Obtaining a high number of hematopoietic stem cells (HSCs) is a major challenge for developing cell therapies for blood diseases. Ex vivo expansion of HSCs involves various factors (cytokines, environment), including low oxygen (O2) concentrations, that reflect the physiological conditions found in specific structures of the bone marrow where HSCs reside. Our team is interested with the study of these low O2 levels for several years and their beneficial effects are currently well established during short-term cultures of cells from bone marrow, cord blood or mobilized in the blood. We sought to confirm and extend these results to poorly studied cells: stem cells from steady state peripheral blood (SSPB). Indeed, these cells represent a possible HSCs source devoted to the therapeutic use, because of their availability and their easy access. Our work has led to the establishment and the optimisation of a procedure, rapid and easy to set up, for CD34+ cells purification from leukoreduction filters (LRFs). The cell quantities and purities, adapted to our further work, together with their functional validation, led us to use these cells as a model for 7-days in vitro cultures performed at very low O2 concentration (0.1%). Cytokine combination assays, allowing the maintenance and the expansion of primitive cells, have revealed a beneficial influence of IL-3 or SCF + TPO additions. These cultures have revealed, comparatively to those performed at 20% O2, a major role of the very low O2 concentrations in the maintenance of quiescent and undifferentiated cells, showing an un- or low-cycling status and able to reconstitute hematopoiesis, consecutively to their injection into NOG mice. However, the molecular and metabolic mechanisms involved in these processes remain unknown
Brunet, de la Grange Philippe. "Régulation de l'hématopoïèse par les basses concentrations d'oxygène : rôles de l'antigène CD34 et du facteur de croissance VEGF165." Bordeaux 2, 2004. http://www.theses.fr/2004BOR21093.
Hematopoiesis, the process of mature blood production from stem cells, is in part regulated by bone marrow oxygen concentrations, which vary from 0 to 5 % (hypoxia). We studied in this work the relationships between cell intrinsic factors involved in the maturation process (CD34 antigen) and their sensitivity to hypoxia, and the effects of molecules inducible by hypoxia (Vascular Endothelial Growth Factor, VEGF) on hematopoiesis. We showed that cultures of CD34+ cells at 1 % O2 induce or stabilize the cd34 gene expression that decreases at 20 % O2. The prolonged maintenance of this expression associated with the long-lasting membrane expression of the protein were correlated with the primitiveness of cells. We also showed that VEGF165 led to the survival of murine stem cells cultured at 1 % O2. This work suggests that hypoxia slows down the differentiation of stem cells by inducing cd34 gene expression, and favours their survival through VEGF165
Ben, Azouna Nesrine. "Etude phénotypique et fonctionnelle des cellules souches mésenchymateuses et hématopoïétiques du sang placentaire en comparaison avec la moëlle osseuse ou le sang périphérique adulte." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR3321.
The mesenchymal stem cells (MSC) are adult stem cells which are at the origin of the ostebiastic lignage cells (O), adipocytes (A) and chondrobiasts (C). The MSC are initially found in the bone marrow (BM) but it also exists there in other tissues as the umbilical cord blood (UCB).Endowed with a regenerative potential, MSC can used in diverse degenerative pathologies in a purpose of tissular repair. Besides, their immunosuppressive properties allowed to envisage their use in a purpose of immunomodulation as during the reactions of transplant against the host in allogenic hematopoietic stem cell transplants (HSC). The essential purpose of this work was to compare the characteristics of the MSC derived from the UCB in comparison to those stemming from the bone marrow (BM)
Sinka, Lidia. "L' enzyme de conversion de l'angiotensine (ACE) dans l'ontogenèse du systeme hématopoïetique de l'embryon et du foetus humains." Paris 7, 2008. http://www.theses.fr/2008PA077108.
Hematopoietic stem cell (HSC) population was previously identified adhering to the aortic endothelium of the human embryo, which is at the origin of definitive hematopoiesis in man. These precursor cells are generated in the paraaortic splanchnopleura (P-Sp): the presumptive region of the hematogenic aorta. To assess the cellular identity of this intraembryonic hematopoetic activity, we have used a novel monoclonal antibody, BB9, that typifies the most primitive HSCs in the adult. BB9 recognizes angiotensin converting enzyme (ACE). ACE is a key component of renin-angiotensin System (RAS), a blood pressure regulator. We show a direct relationship between expression of ACE and emergence of HSC in all hematopoietic organs during human development and that in vitro and in vivo hematopoietic abilities are restricted to ACE+ HSC. Furthermore, from 19 until day 26 of gestation, BB9 identifies rare CD34"CD45" cells in the hemogenic P-Sp, responsible of in vitro hematopoietic ability. Between 27 and 40 days of development, when HSC clusters are present in ventral side of dorsal aorta, ACE is expressed on intraaortic HSC clusters and surrounding aortic endothelial cells. These results are consistent with the hypothesis of a BB9+CD34" CD45" hemangioblastic precursor migrating from the P-Sp toward the ventral aorta, to give rise to CD34+ intraaortic HSC clusters. These studies demonstrate that ACE is a novel marker of primitive HSCs in the adult and in the human embryo. Moreover, our preliminary results from in vitro experiments with RAS inhibitors indicate that ACE and RAS have direct regulatory effects on developmental hematopoiesis
Vinsonneau, Ulric. "Traitement du myélome par double intensification avec autogreffe de cellules souches périphériques CD34+ : à propos de 19 cas, étude non randomisée." Bordeaux 2, 1999. http://www.theses.fr/1999BOR2M040.
Desplat, Vanessa. "Effets des médiateurs lipidiques au cours de l'hematopoiése humaine." Limoges, 2000. http://www.theses.fr/2000LIMO107G.
Caux, Christophe. "Étude du rôle du TNFα sur la régulation de la myélopoïèse humaine in vitro." Lyon 1, 1992. http://www.theses.fr/1992LYO1H002.
Foudi, Adlen. "Etude de la fonction et de la régulation du récepteur CXCR4 dans l'hématopoïèse." Paris 7, 2006. http://www.theses.fr/2006PA077100.
CXCR4 receptor and ils ligand SDF-1 are involved in numerous biological processes ranging from cell migration, proliferation and survival. The downregulation of CXCR4 expression or its decreased function results in hematopoietic stem cells mobilization. CXCR4 receptor is also involved in malignacy, tumor metastases, HIV entry and in WHIM and WAS (Wiskott-Aldrich syndrome) syndromes. Using an in vivo hematopoietic reconstitution assay of lethally irradiated mice, we demonstrated that CXCR4-null fêtai liver cells exhibited a dramatic radioprotection deficiency related to a reduced homing of maturing myeloid cells. The homing of CXCR4-/- and CXCR4+/+ progenitor cells are similar but CXCR4-/- chimeric mice displayed a high circulating number of progenitors during several month after transplantation. These results indicate that CXCR4 receptor is a key regulator of progenitor cells maintaining to the bone marrow microenvironment. Moreover, we show that circulating human primitive CD34+ cells exhibited a high level of intracellular pool of CXCR4 receptor. This pool is associated with the expression of several endosomal markers suggesting an important constitutive endocytosis of CXCR4 in thèse cells. These data indicate that the distribution of CXCR4 between cell surface and cytosol may be important in the mecanisms involved in HSC mobilization. A reduced migration of cells from WAS patients have been characterized. Here we show that WASP-null mice exhibited a slight thrombopenia associated with an elevated number of proplatelets in their bone marrow. Maturing megakaryocytes from WASP-null mice displayed a reduced in vitro migration toward SDF-1 chemokine. These results suggest that WASP protein is involved in megakaryocytic SDF-1 signaling. This mechanism may be responsible for megakaryocytes homing to specific vascular niches in the bone marrow microenvironment, priorto platelets shedding
Mayol, Jean-François. "Etude du potentiel hématopoïétique des cellules de foie." Université Joseph Fourier (Grenoble), 2007. http://www.theses.fr/2007GRE10132.
Many recent studies reported that ce Ils with an hematological potential could be identified and isolated within adult solid organs. On the basis of this new concept, we have evaluated the hemato logical potential of liver cells in order to replenish a deficient hematopoiesis. Ln the first part ofthis work, the in vitro hematological potential was evaluated and CFU-GEMM, CFU-GM and BFUe were scored after plating liver cells in a semi-solid medium. We demonstrated that this potential was restricted to the CD34+ CD45" liver cell sub-population. Immunophenotyping and transcriptomics showed that these cells are not hematopoietic in origin, and that colonies derived from liver ce Ils synthesized a high rate of embryonic and fetal hemoglobin. The hematopoietic potential of liver ce Ils is relatively low but it could be amplified using a co-culture model with mesenchymal stem cells. Ln the next part, we showed that the administration of unfractionated liver cells to total body irradiated non-human primates failed to fully reconstitute the hematopoiesis, but it led to a transient granulocytic reconstitution that was not observable in control animais. The injection of liver cells in immunodeficient NOD-SCID mice led to a medullar microchimerism. It demonstrates that liver cells are capable of engrafting into irradiated mice and pro duce CD4S+ cells. Finally, we have developed a cell culture model to evaluate the radiosensitivity of non-cIonogenic cells such as liver cells
Malfuson, Jean-Valère. "Rôle de la niche mésenchymateuse dans la régulation du phénotype SP des progéniteurs hématopoïétiques humains." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00956760.
Abou, Ezzi Grazia. "Immunomodulation de la réponse des lymphocytes T CD4+ par les ostéoclastes." Nice, 2012. http://www.theses.fr/2012NICE4052.
Osteolysis is a hallmark of chronic inflammatory diseases due to an over differentiation and activity of osteoclasts (OCLs), mainly induced by activated/ memory CD4+ T cells. OCLs are derived from the monocyte lineage and in inflammatory condition, they can also arise from dendritic cells. OCLs have been described to be a major player in maintaining hematopoietic stem cells (HSCs) in their medullar niches, and contribute to their mobilization under stress condition. During my PhD, I was interested in studying the role of OCLs on CD4+ T cells. First, I focused on the capacity of OCLs to present antigen and activate CD4+ T cells. We showed, for the first time, that both subsets of OCLs can present antigens and activate CD4+ T cells with a difference in polarizing T cells. OCLs derived from normal bone marrow polarize T cells toward regulatory T cells (Foxp3+), whereas OCLs derived from DCs induce inflammatory T cells (INFγ+, TNFα+). In an interesting way, OCLs differentiated from inflammatory bone marrow fail to induce regulatory CD4+T cells, demonstrating that the bone marrow environment is essential in the control of the immunomodulatory effect of OCLs. Since memory T cells represent a major CD4+ T cell population in the bone marrow and are maintained in specialized niches in quiescent state, the second part of my thesis was to define if OCLs may play a role in mobilizing those cells, as they do for HSCs. We demonstrated that OCLs control the mobilization of central memory T cells from the bone marrow by modulating the phenotype of the mesenchymal cells forming the niches. This study present a new vision of the multiple functionalities of OCLs, going from activating T cells as any other antigen presenting cells to controlling the mobilization of memory T cells from the bone marrow to the periphery. Those newly defined functions of OCLs may contribute to generate new therapeutic approaches to limit the propagation of autoimmune/inflammatory diseases
Mouly, Enguerran. "Optimisation chez l' homme du transfert de gènes dans les cellules souches/progéniteurs hématopoïétiques et les cellules du système immunitaire et applications." Paris 7, 2005. http://www.theses.fr/2005PA077113.
Blache, Céline. "Développement et fonction des lymphocytes T régulateurs : rôle du corécepteur CD4, du G-CSF et des anti-TNF." Rouen, 2009. http://www.theses.fr/2009ROUES024.
Treg play a major role in the control of physiological immune responses. We have studied the role of CD4 coreceptor in the Treg biology. In CD4 mice, we observed Treg population in the thymus and the periphery where the frequency is twice as compare to control mice. We have studiez, in Human, the influence of two graft types of peripherical blood stem cell transplantation on Treg compartment and the evolution of Treg population during anti-TNF treatment on Rheumatoid Arthritis (RA). The Treg frequency is significantly lower in PBSC and is associated with a loss of CD62L expression. In RA, we have studied the evolution of Treg in blood during 2 anti-treatments. We did not observe impact between 2 treatments on the evolution of Treg blood. These results bring new insight in Treg development and their implication in human pathology
Meignin, Véronique. "Maladie du greffon contre l'hote : étude de la plasticité des cellules souches hématopoïétiques in situ : étude de la de population régulatrice CD24+CD25+." Paris 7, 2005. http://www.theses.fr/2005PA077208.
The graft versus host disease (GVHD) is a frequent and often lethal complication of allogeneic Bone Marrow Transplantation (BMT). The pathophysiology of this disease is not yet completely understood. We first studied the plasticity of the hematopoietic stem cells in the digestive epithelial cells of sexmismatched allograft patients, presenting an acute GVHD. We have analyzed the donor or récipient origin of the glandular epithelial cells by a FISH XY method combined with immunostainings on the same slide. By contrast to other studies, we have not found plasticity, the patient having or not an acute GVHD. In a second part, we evaluated whether recovery of CD4+CD25high T cells, a subset known to have suppressive activity on effectors T cell, might be linked to the establishment of full donor / recipient tolerance. The frequency of this subset was determined by Fluorescence Activated cell Sorter (FACS) analysis and thé expression levels of Foxp3 mRNA, a specific transcription factor, vvere assessed by quantitative real-time polymerase chain reaction (PCR). The low number of Foxp3 expressing CD4+CD25high T cells was not a specific default of this compartment but a conséquence of global CD4+ T cell lymphopenia after allogeneic BMT. Moreover, levels of Foxp3 mRNA in CD25+ T cells compartment do not allow predicting the development of GVHD in the long term
Noel, Grégory. "Lymphocytes T régulateurs : rôle dans le contrôle de la maladie du greffon contre l'hôte et obtention à partir de lymphocytes T naïfs." Rennes 1, 2009. http://www.theses.fr/2009REN1B075.
Trenado-Bauquet, Aurélie. "Utilisation des propriétés immunosuppressives des lymphocytes T CD4+CD5+ dans l' alloréactivité pour contrôler la maladie du greffon contre l' hôte (GVH)." Paris 6, 2005. http://www.theses.fr/2005PA066254.
Diaz, Rodriguez Yildian. "La différentiation in vitro des cellules dendritiques plasmacyto des partir de cellules CD34+ de sang de cordon, un outil thérapeutique pour augmenter l'activité́ antitumorale des cellules NK." Thèse, 2017. http://hdl.handle.net/1866/19443.
NK cells immunotherapy is a promising treatment for different human cancers. An effective approach to stimulate NK cells has been the use of activated plasmacytoid dendritic cells (pDC). NK cell activated by pDC develops a strong cytotoxic response against pre-B acute lymphoblastic leukemia (ALL) cell lines in vitro and in vivo. However, the use of pDC in the clinic has limitations because of its low frequency. One suitable strategy is the differentiation of CD34+ progenitors using different cytokines and chemokines. Recently, it has been demonstrated that antagonists of aryl hydroxyl receptor (AhR) increase the number of pDC obtained after culture of CD34+ cells. Nevertheless, the ability of these in vitro differentiated pDC to induce NK cells activation has not been well documented. In this study, it was showed that activated in vitro differentiated pDC present different characteristics than adult pDC, like a lower expression of activation markers and IFNalpha secretion, but their capacity to stimulate NK cells was similar to that observed in adult pDC. In addition, NK cells activated by in vitro differentiated pDC showed a strong cytotoxicity against the pre-B ALL cell line REH suggesting its effectiveness to treat ALL patients.
Trottier, Jessica. "Expansion des mégacaryocytes par HoxB4 pour accélérer la reconstitution plaquettaire." Thèse, 2014. http://hdl.handle.net/1866/12266.
Haematopoietic stem cell (HSC) transplantation is the most efficient treatment against a number of cancers or other disorders of the hematologic system. Prior to HSC transplantation, patients are exposed to high doses of radiotherapy and/or chemotherapy to eliminate malignant cells. However, these treatments result in a state of aplasia, particularly in thrombocytopenia, which is characterised by very low blood platelet counts. Platelets produced by megakaryocytes (MK) are essential components of the blood system and play a critical role in the prevention of bleeding. Thus a low platelet blood level is a major complication and contributes significantly to transplant related mortality. At present, regular infusion of platelets isolated from healthy donors is the treatment of choice for thrombocytopenia. However, this is cumbersome for patients as well as donors and, in many instances results in platelet refractoriness due to the generation of auto-antibodies against disparate HLA molecules expressed on donor platelets. Therefore, the development of strategies to accelerate MK production and thus platelet reconstitution post HSC transplant would represent a major advance. It has already been shown that HoxB4 expands HSC and multipotent progenitors (CFU-GEMM) that give rise to megakaryocytes (MK). Thus HoxB4 is a great candidate for in vitro MK progenitor expansion. However, the short half-life of HoxB4 protein prompted us to generate a second generation of HoxB4 proteins with greater intracellular stability. We therefore studied the capacity of wild type (WT) and HoxB4 with 3 substitutions (1423 (HoxB4L7A), 1426 (HoxB4Y23A) and 1427 (HoxB4Y28A) resulting in a longer protein half-life to expand HSC as well as MK progenitors. Retroviral-mediated expression of HoxB4Y23A and HoxB4Y28A proteins showed a greater expansion of murine MK progenitors, in comparison with HoxB4WT or HoxB4L7A proteins or GFP control. We also evaluated the ability of HSC expressing second generation HoxB4 to generate platelets in a murine model. Our results show that retroviral-mediated transduction of second generation HoxB4 in murine HSC does not provide a significant advantage over HoxB4WT in platelet reconstitution in mice. Interestingly, treatment of CD34+ cells derived from cord blood showed only marginal effect of HoxB4WT or second generation HoxB4 soluble recombinant proteins when cultured under conditions optimized for megakaryocyte differentiation. Unexpectedly, CD34+ cells derived from mobilized peripheral blood of myeloma patients showed a significant increase in MK progenitor differentiation in the presence of TAT-HoxB4WT when cultured in expansion medium for HSC. Thus, HoxB4 holds promise in autologous HSC transplantation for the treatment of thrombocytopenic patients.
Tremblay-Laganière, Camille. "Thérapie génique ciblant CD33 dans les cellules souches hématopoïétiques, une approche innovatrice pour le traitement de la leucémie myéloïde aiguë." Thèse, 2018. http://hdl.handle.net/1866/22328.
Gauthier, Simon-David. "Impact de la maladie du greffon contre l’hôte sur la reconstitution immunitaire suite à une transplantation allogénique de cellules souches hématopoïétiques." Thèse, 2015. http://hdl.handle.net/1866/13542.
Hematological cancers are currently treated with allogeneic hematopoietic stem cell transplantation (ASCT). Unfortunately, graft-versus-host disease (GVHD) greatly limits the health benefits of this procedure, as it is the main cause of mortality post-ASCT. GVHD damages various organs and delays the immune reconstitution of T lymphocytes (TL), which increases the risk of infections and relapse. Thus, developing new treatments modulating the immune reconstitution following ASCT would greatly enhance survival of the transplanted patients. TL can be regenerated by two ways: de novo production of TL by thymopoiesis; or homeostatic proliferation (HP), which consists of rapidly expanding mature TL already present in the graft. HP requires two crucial signals: interleukin-7 (IL-7) and self-antigen presentation by dendritic cells (DC) via the major histocompatibility complex (MHC) I for CD8+ TL and MHC II for CD4+ TL. During ASCT however, chemotherapy and GVHD induce damage to the thymus making thymopoiesis inefficient, and thus immune reconstitution relies almost entirely on HP of TL. The objective of this thesis was to understand how GVHD affects TL reconstitution. Using a mouse model, we demonstrate that CD4+ TL fail to undergo HP when transferred in GVHD hosts due to low levels of IL-7 and reduced numbers of DCs. Moreover, the loss of DCs is mostly caused by reduced levels of Stromal Derived Factor-1 alpha (SDF-1α) and the absence of DC progenitors in the bone marrow of mice suffering from GVHD. Treating GVHD hosts with SDF-1α resulted in increased DC counts and, when administered in combination with IL-7, significantly improved HP of CD4+ TL. Unlike CD4+ TL, administration of IL-7 alone was sufficient to restore HP of CD8+ TL in GVHD mice and this, regardless of the presence of DCs. These differences could be explained by two reasons: 1) MHC I expression is not limited to DCs but is expressed by stromal cells from the recipient, which is sufficient to promote HP in CD8+ TL and 2) CD8+ TL respond to lower doses of systemic IL-7 in comparison to CD4+ TL. In conclusion, these results can lead to future translational studies on the therapeutic potential of SDF-1α and IL-7 in the immune reconstitution of grafted patients.
Cournoyer, Élise. "Évaluation de l'activité anti-leucémique des cellules T traitées par photodéplétion au TH9402." Thèse, 2016. http://hdl.handle.net/1866/18861.