رسالة جامعية
Deleterious effect of bone marrow resident macrophages on hematopoietic stem cell response to ionizing radiations ; Rôle délétère des macrophages résidents de la moelle osseuse dans la réponse des cellules souches hématopoïétiques aux radiations ionisantes
| العنوان: | Deleterious effect of bone marrow resident macrophages on hematopoietic stem cell response to ionizing radiations ; Rôle délétère des macrophages résidents de la moelle osseuse dans la réponse des cellules souches hématopoïétiques aux radiations ionisantes |
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| المؤلفون: | Chalot, Marion |
| المساهمون: | Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité, Paul-Henri Roméo, Stéphanie Moreno |
| المصدر: | https://theses.hal.science/tel-03624903Test ; Médecine humaine et pathologie. Université Paris Cité, 2021. Français. ⟨NNT : 2021UNIP7068⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Total Body irradiation, CD169+ macrophages, Hematopoietic stem cells, Reactive Oxygen Species (ROS), Nitric oxide, Peroxynitrites, Macrophages CD169+, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | With more than half of patients benefiting from it, radiotherapy is one of the most used method in cancer treatment. Despite its efficiency to eradicate tumors, its main inconvenience is the toxicity it can bring to surrounding healthy tissues. In bone marrow, which contains the hematopoietic stem cells (HSC), this toxicity can be highly harmful. Indeed, HSC are responsible for life-long generation of blood cells emphasizing the importance to preserve them. Those cells are localized in a cellular microenvironment, the hematopoietic niche, which is essential for HSC protection and to maintain their integrity. Within this niche, bone marrow resident macrophages expressing the CD169 surface marker have been shown to play a role in the maintenance of HSC in their niche, but also in their protection toward an oxidative stress. Therefore, the aim of my project was to define the role of resident bone marrow macrophages in HSC response to a 2 Gy total body irradiation (TBI), dose commonly used in fractionate radiation therapy. To address this question, I have used two models of mice depleted in CD169+ macrophages (CD169+ Mϕ): a pharmacological model (clodronate-liposomes) and a genetic model (CD169DTR/+ mice). In both models, I have shown that CD169+ Mϕ depletion before irradiation leads, short term after TBI, to a less important diminution of the HSC pool, coupled with a decrease in their apoptotic rate and an absence of reactive oxygen species (ROS) that are generally induced by radiations. Longer term after irradiation, this absence of CD169+ Mϕ allows a complete recovery of a functional pool of HSC. Taken together, those results demonstrate that the presence of resident macrophages during an irradiation has a deleterious effect by diminishing the HSC pool within the bone marrow. To highlight the mechanism(s) leading to this deleterious effect, I investigated the direct response of CD169+ Mϕ to irradiation, focusing on the oxidative stress response. I have observed that TBI induces an increase of the proportion of ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | French |
| العلاقة: | NNT: 2021UNIP7068; tel-03624903; https://theses.hal.science/tel-03624903Test; https://theses.hal.science/tel-03624903/documentTest; https://theses.hal.science/tel-03624903/file/CHALOT_Marion_va2.pdfTest |
| الإتاحة: | https://theses.hal.science/tel-03624903Test https://theses.hal.science/tel-03624903/documentTest https://theses.hal.science/tel-03624903/file/CHALOT_Marion_va2.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.F5B167CD |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |