Tesi sul tema "In cellulo and in vivo models"
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Fischer, Jared Michael. "Mouse Models of Mutation in vivo". University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1227214862.
Passeri, Elodie. "Use of nanoliposomes rich in omega-3 for the prevention of neurodegenerative diseases : bioavailability in vivo and in cortical neurons". Electronic Thesis or Diss., Université de Lorraine, 2021. https://docnum.univ-lorraine.fr/ulprive/DDOC_T_2021_0337_PASSERI.pdf.
Alzheimer's disease (AD) is the most common cause of neurodegenerative disease and represents a major public health issue worldwide. Many therapeutic strategies have been explored for several decades, however, there is still no curative treatment and the priority remains prevention. In this thesis work, we focused on the preventive approach based on lipids, in particular omega-3 polyunsaturated fatty acids (n-3 PUFAs). N-3 PUFAs play an important role in the development, maintenance and function of the brain, and they have been the subject of particular interest in the prevention of cognitive deficits associated with neurodegenerative diseases. The objective of this work is to study the functionality and bioavailability of nanoliposomes (NL) rich in n-3 PUFAs, in order to assess their neuroprotective potential to develop new preventive strategies in aging-related diseases such as AD. To do this, a green extraction technique was used to prepare NL, from natural resources from salmon lecithin rich in n-3 PUFA. This thesis is based on three parts. The first part is devoted to a bibliographical review of new techniques to facilitate the access of molecules to the brain. NL shows a promising role, being able to improve the transport of molecules across the blood-brain barrier and reach relevant brain regions. In the second part of this work, the bioavailability of NL rich in n-3 PUFA was studied in a primary culture of cortical neuronal cells from rat embryos and in a mouse model. This study shows for the first time the brain bioavailability of NL rich in n-3 PUFA in in vitro and in vivo models. Finally, in the third part of this thesis, the physicochemical properties and transfer mechanisms of NL were studied in a primary culture of cortical neurons. These results provide new information on the interaction between NL and neurons and are promising with regards to the use of NL rich in n-3 PUFA, opening up new possibilities in the development of preventive and neuroprotective therapeutic strategies for neurodegenerative diseases such as AD
Rose, Nicolas. "New ex vivo models to study the mechanical interplay between muscle cells and their microenvironment". Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS440.
Ex vivo systems are under increasing interest for bioethical, legal and financial stakes. To study muscle function and regeneration, medical research requires functional analysis platforms for mature myotubes and unconventional muscle stem cells (MuSCs) culture tools integrating mechanical consraints. During my doctoral works, a 3D myotube culture chip with contraction monitoring capacity has been developed. Combining photopatterning technology and microsubstrate design allowed to obtain high culture yield in controlled physical and chemical microenvironment. Spontaneous contractions of human primary myoblast-derived 3D myotubes has been observed, their generated forces measured and their contraction pattern characterised. The impact of 3D culture on nuclear morphology has been analysed, confirming organizational similarities betaween obtained 3 myotubes and in vivo myofibers. Moreover, LMNA-related Congenital Muscular Dystrophy has been modelled in 3D mutants myotubes displaying typical laminopathy phenotype. Finally, MuSCs has ben cultured on hydrogels, demonstrating the effect of niche elasticity variations on MuSCs activation during muscle regeneration
BAZZINI, CHIARA. "STUDY OF MOLECULAR MECHANISMS AND NEW STRATEGIES AGAINST A CYTOTOXICITY AND NEUROINFLAMMATION IN EX VIVO CELLULAR MODELS FROM ALZHEIMER’S DISEASE PATIENTS". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2021. http://hdl.handle.net/10281/306480.
Alzheimer's disease (AD) is a major public health concern and has been identified as a priority for research in Life Science. The two core pathological hallmarks of AD are extracellular amyloid plaques and intracellular neurofibrillary tangles which underlie microglial and neuronal damage, neuroinflammation and cognitive impairment. Soluble oligomers are the most toxic species of β-amyloid (Aβ) and interact with several protein kinases such as Ras/MAPK and PI3K/AKT pathways, which regulate many cellular processes and cognitive functions. These pathways mediate Aβ toxicity, regulating some molecular mechanisms involved in neuronal degeneration such as cytoskeletal impairment, glutamate excitotoxicity and neuroinflammation. In the last years much attention has been focused on the potential role of natural compounds as neuroprotective agents. Hop (Humulus Lupulus) contains flavonoids, aromatic molecules which have antioxidant, anti-inflammatory and anti-atherogenic properties. In fact, hop extract has anti-aggregating effects on Aβ, and it seems to prevent its production in cultured cells. Aβ induces also the activation of the pattern recognition receptor Nod-like receptor protein 3 (NLRP3) inflammasome complex in microglia and the consequent release of proinflammatory cytokines, playing a pivotal role in AD-associated neuroinflammation. NLRP3 activation results in the release of inflammatory mediators, including ASC protein complexes (ASC specks), IL-1β and IL-18, that facilitate Aβ deposition and neuroinflammation in a self-feeding pathogenic loop. Since specific therapeutical strategies are still lacking, the dampening of the inflammasome assembly and activation could be a new strategy for AD. The overall focus of this study is to investigate molecular mechanisms involved in neurodegenerative diseases and in neuroinflammation, using peripheral ex vivo cellular models from AD, to check new potential therapeutical targets. In order to characterize the complex interactions among Aβ, MAPK and AKT signaling, we used fibroblasts from sporadic AD patients with different disease severity. To evaluate any molecular mechanisms that could prevent or modulate Aβ-induced toxicity, the potential cytoprotective effects of Hop extract and related intracellular signaling were also investigated. Fibroblasts provide a useful cellular model for studying AD, since they could be differentiated into patient-specific neural cell lines, using iPSC technologies. Moreover, particular interest was given to NLRP3-inflammasome activation pathway. We investigated the involvement of NLRP3 inflammasome activation on intracellular pathways and their downstream targets, using a combination of in vitro studies and patient-derived samples. In particular, we used macrophage-derived THP-1 human monocytes and peripheral blood mononuclear cells (PBMC)-derived monocytes from healthy control (HC) subjects and AD patients, to analyse phagocytosis, autophagy and apoptosis modulation and the effects of the nucleoside reverse transcriptase inhibitor Stavudine (D4T), that reduces NLRP3 inflammasome activation blocking the purinergic receptor P2X7R. Furthermore, we analyzed the NLRP3 inflammasome pathway and the role of the selective NLRP3 inhibitor CRID3, to compare the effects of inflammasome inhibition through two different mechanisms. At this purpose, HC and AD-derived monocytes were differentiated into microglia-like cells (MDMIs) and characterized for myeloid surface and intracellular proteins expression. Key microglia functions such as inflammatory cytokines release, Aβ phagocytosis and degradation were evaluated upon exposure to NLRP3 inflammasome activators with or without CRID3. MDMIs reflected many features of microglia and, as fibroblasts-derived iPSCs, they are attractive cellular models helpful to understand AD pathogenesis, identify therapeutic targets and allow large-scale drug screening of the novel therapeutic candidates.
Zangrossi, Manuela. "Study of the extra-telomeric functions of telomerase in in vitro and in vivo models". Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3426233.
Il mantenimento dei telomeri, necessario per la proliferazione illimitata delle cellule tumorali, è esercitato dalla telomerasi, un complesso ribonucleoproteico contenente una trascrittasi inversa specializzata, codificata dal gene TERT, che utilizza un templato ad RNA per sintetizzare nuove sequenze telomeriche, svolgendo quindi un ruolo critico nella formazione e nella progressione dei tumori. TERT viene infatti solitamente represso in normali cellule somatiche, mentre è rilevabile nella maggior parte dei tumori. Studi recenti hanno suggerito che TERT è coinvolto in altre funzioni cellulari e può contribuire alla carcinogenesi anche attraverso meccanismi indipendenti dal mantenimento dei telomeri, quindi la sua inibizione potrebbe rappresentare una strategia promettente per migliorare il trattamento antitumorale, al di là dell’effetto sui telomeri. I possibili effetti terapeutici di BIBR1532 (BIBR), un inibitore specifico del TERT, sono stati valutati in diversi contesti cellulari, ma non sono attualmente disponibili dati ottenuti su modelli di neoplasie delle cellule B sia associate al virus di Epstein-Barr (EBV) che virus-indipendenti. Lo scopo di questo studio era di caratterizzare gli effetti biologici dell'inibizione di TERT a breve termine da parte del BIBR su linee cellulari linfoblastoidi immortalizzate da EBV (LCL) e su modelli in vitro di linfoma di Burkitt (BL); inoltre, sono stati studiati gli effetti del trattamento con BIBR a breve termine in vivo negli embrioni di zebrafish. I risultati ottenuti hanno dimostrato che l'inibizione a breve termine di TERT da parte di BIBR, in modelli in vitro di tumori delle cellule B, ha portato a una diminuzione della proliferazione cellulare, all'accumulo di cellule nella fase S e infine all'aumento dell'apoptosi. L'arresto del ciclo cellulare e l'apoptosi, conseguenti all'inibizione di TERT a breve termine, erano associati e probabilmente dipendenti dall'attivazione della risposta al danno del DNA, come evidenziato dall’aumento dei livelli di γH2AX e dall'attivazione dei pathway di ATM e ATR. L’analisi della media e del range di lunghezza dei telomeri e dei foci di danno al DNA ha indicato che la risposta al danno attivata in seguito all’inibizione TERT a breve termine non era legata a disfunzioni telomeriche, suggerendo quindi che TERT, oltre a stabilizzare il telomero, può proteggere il DNA tramite meccanismi telomero-indipendenti. In particolare, LCL-TERT positive trattate con BIBR in combinazione con fludarabina o ciclofosfamide hanno mostrato un aumento significativo del numero di cellule apoptotiche rispetto a quelle trattate con agenti chemioterapici da soli. In accordo con i risultati in vitro, l'inibizione a breve termine di Tert da parte del BIBR in embrioni di zebrafish ha ridotto la proliferazione cellulare, indotto un accumulo di cellule nella fase S, aumentato il tasso di apoptosi e innescato l'attivazione della risposta al danno al DNA. Questi effetti non erano legati a disfunzioni telomeriche, poiché il range di lunghezza dei telomeri non era influenzato dal trattamento a breve termine con BIBR e i foci di danno al DNA erano distribuiti casualmente, piuttosto che localizzati in modo specifico sui telomeri. Tutti questi effetti erano specificamente associati all'inibizione di Tert poiché il trattamento con BIBR non mostrava alcun effetto negli embrioni di zebrafish Tert-negativi. Nel complesso questi dati dimostrano che l'inibizione del TERT compromette la proliferazione cellulare e induce effetti pro-apoptotici non associati a disfunzioni telomeriche, rafforzando il concetto che TERT esercita di per sé funzioni pro-tumorali indipendenti dalla lunghezza del telomero e quindi supportando l'introduzione di inibitori di TERT per integrare le attuali modalità di trattamento antitumorale.
Ronayne, Rachel E. "Human Ependymin-1 Neurotrophic Factor Mimetics Reduce Tau Phosphorylation and Cellular Apoptosis in Vitro and in Vivo in Alzheimer’s Disease Models". Digital WPI, 2008. https://digitalcommons.wpi.edu/etd-theses/1018.
Lu, Yen-Zhen. "The effects of 670nm light on retinal Müller cell gliosis following retinal stress or injury: exploring the underlying cellular mechanisms using in vivo and in vitro models". Phd thesis, Canberra, ACT : The Australian National University, 2018. http://hdl.handle.net/1885/154729.
Toutain, Hervé. "Développement et caractérisation de modèles expérimentaux pour l'étude ex-vivo et in-vitro de la cellule tubulaire proximale de rein de lapin". Rouen, 1989. http://www.theses.fr/1989ROUES036.
Sibeko, Sengeziwe. "The impact of macrophage inflammatory protein-3 alpha and other innate immune markers on susceptibility/resistance to HIV infection in the female genital tract mucosa using cellular and ex vivo tissue models". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:a7ecf529-b94e-492f-8374-675cb495ef05.
Body, Simon. "Physiopathologie du lymphome à cellules du manteau : de la mécanistique aux modèles précliniques". Thesis, Normandie, 2017. http://www.theses.fr/2017NORMC419/document.
Mantle cell lymphoma (MCL) is a mature malignant hemopathy, belonging to the non-Hodgkin's lymphoma family. The MCL is characterized by the translocation t(11;14)(q13;q32) which causes an aberrant expression of cyclin D1. It is a rare disease but at high risk of relapse, and it is most often incurable due to the appearance of chemoresistant clones. The acquisition of resistance is intimately linked to the interactions between the tumor cells and their microenvironment. In order to mimic, in the most relevant way, these interactions, we have implemented a mouse xenograft model using the MCL cell lines JeKo1, REC1, Z138 and Granta-519 which we have modified so that they express a fluorophore (GFP or m-cherry) and / or the gene encoding the luciferase. After injection to the mice of the luciferase substrate, luciferin, we are able to follow over time the tumor progression. We can also assess the degree of tumor infiltration in bone marrow, spleen, brain and blood after euthanasia of animals, by flow cytometry and immunocytochemistry. This model allowed us to show the therapeutic interest of an inhibitor of exportin 1 (XPO1): the KPT 330 (or selinexor) which is able to contain cyclin D1 only on the nuclear level. We have shown that the subcellular localization of cyclin D1 is mainly cytoplasmic in some LCM (2/7) cell lines and in a number of patients (6/42, 14%), and is associated with a high potential Invasion, migration and an aggressive phenotype. Moreover, thanks to this model, we have been able to objectify the in vivo lack of efficacy of agonists to β-type estrogen receptors (ER β). These receptors, present on B lymphocytes, were thought to inhibit cell proliferation and cause cell death by apoptosis. The use of two ER β agonists, diarylpropionitrile (DPN) and ERB-041 showed an absence of effect of these molecules, when the tumor cells are in contact with their microenvironment. On the other hand, in order to better understand the mechanisms of resistance to chemotherapies, we studied the resistance of the REC-1 cell line treated with genotoxic agents. We have shown that this line has an abnormality of cyclin D1 degradation associated with decreased activity of the 26S proteasome. Finally, we have shown in preliminary work that the fused in sarcoma protein (FUS) could, when associated with cyclin D1, be able to regulate the repair pathways of DNA damage. Abnormalities of these pathways induce a great genetic instability responsible for the escape of tumors to treatments, the targeting of FUS could therefore be of therapeutic interest.Taken as a whole, these results reinforce or invalidate the interest of certain therapeutic targets in the hope of continuing to improve the management of patients. They also provide a tool for evaluating new molecules in a murine model that takes into account the interactions between the tumor cell and its microenvironment
Obermaier, Carolin Dominique [Verfasser], e Rejko [Akademischer Betreuer] Krüger. "Identification of the underlying mechanism of the c.192G>C mutation in the DJ-1 gene and functional characterisation in patient-based cellular models of Parkinson’s disease ex vivo / Carolin Dominique Obermaier ; Betreuer: Rejko Krüger". Tübingen : Universitätsbibliothek Tübingen, 2015. http://d-nb.info/116523498X/34.
Obermaier, Carolin [Verfasser], e Rejko [Akademischer Betreuer] Krüger. "Identification of the underlying mechanism of the c.192G>C mutation in the DJ-1 gene and functional characterisation in patient-based cellular models of Parkinson’s disease ex vivo / Carolin Dominique Obermaier ; Betreuer: Rejko Krüger". Tübingen : Universitätsbibliothek Tübingen, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-649120.
Alaa, El Din Ferdos. "Le syndrome de Rendu-Osler-Weber : aspects génétiques, moléculaires et épidémiologiques". Thesis, Poitiers, 2015. http://www.theses.fr/2015POIT2260/document.
Hereditary hemorrhagic telangiectasia (HHT) is a rare disease (1/10.000). Its incidence is higher in certain geographic areas including the Poitou-Charentes region (1/1000). This autosomal dominant disease is caused by mutations in one of three identified genes ENG, ACVRL1 and SMAD4 encoding BMP pathway proteins specially expressed in endothelial cells. The increasing number of mutations detected in patients and the variable expressivity of certain mutations has taken us to determine the consequences of mutations to establish a genotype/phenotype correlation. This correlation is important for genetic counseling and obviously for prenatal diagnosis. In this context, we investigated the effects of several mutations at the cellular and molecular levels. The deleterious impact of these mutations on the protein and/or RNA splicing was evaluated. We have shown that for the 23 mutations of ACVRL1: 1) 18 missense mutations affect the functionality of the protein in response to BMP9 and 3 are polymorphisms, 2) exonic mutation c.733A>G (p. Ile245Val) affects the splicing of the exon 6, 3) mutation c.1048+5G>A in intron 7 off the consensus site induces an aberrant splicing of exon 7. Concerning the ENG, we analyzed 4 mutations and we showed that the mutation c.1088G> A (p.Cys363Tyr) has an impact on the activity of the receptor and that the mutations c.1134G> A (p.Ala378Ala) and c.1060C> T (p.Leu364Leu) inhibit the splicing of exon 8. This work shows the importance of the comprehensive study of any new mutation by in silico, in vitro and in cellulo studies at different cellular levels. The in vivo studies can further complement and support the experimental strategy that we followed
Groult, Jessica. "Expansion ex vivo des Cellules Tumorales Circulantes comme modele de pharmacologie predictive des cancers". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS236/document.
The emergence of targeted therapies in cancer treatment has made essential the development of more specific and sensitive markers for monitoring patients. At the invasive stage, tumor cells can pass to blood. These cells are called Circulating Tumor Cells (CTC). CTCs are accessible through a simple blood test, avoiding invasive biopsies. Moreover, they represent the only residual tumor after treatment. It is why CTCs are a very active center of research with more than 400 clinical trials involving these cells as biomarkers. These tests provide important information on the risk of recurrence or metastatic progression and aim to manage in real time the therapeutic conduct. But the CTC potentially metastatic represents only a fraction very minority of these circulating cells. Existing technologies, mainly based on simple enumeration, are not enough to effectively guide therapeutic strategy. This project has evaluated a set of criteria to make appropriate therapeutic decisions, adapted to each patient, and able to measure the effectiveness of treatments. This project will focus on melanoma. Evolution stages of this cancer are well defined, and in advanced stages, the risk of developing metastases is very high and the early detection is an important issue. Moreover, CTC could be is an interesting tool to test the effectiveness of these new treatments
Belcher, Joyce Yvonne. "Bone Cell Autonomous Effects of Osteoactivin In Vivo". Diss., Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/183061.
Ph.D.
Osteoactivin (OA) is a type I transmembrane glycoprotein initially identified in bone in 2002. The protein is synthesized, processed and heavily glycosylated by osteoblasts. Its expression is associated with increased osteoblast differentiation and matrix mineralization. To determine the role of OA in skeletal homeostasis in vivo. we utilized a mouse model with a natural mutation in the osteoactivin gene. This mutation is due to a premature stop codon, which results in the generation of a truncated 150 amino acid OA protein. This animal, which we will refer to as OA mutant, was shown by ìCT and histomorphometric analysis to have increased bone volume, trabecular thickness, and trabecular number compared to wild-type (WT) mice at 4 weeks of age, which is a time at which bone formation is most active. Histological analysis of long bones stained with TRAP (tartrate resistant acid phosphatase) and colorimetric analysis of serum TRAP 5b levels indicated that the numbers of osteoclasts are significantly increased in OA mutant samples. Interestingly, although the numbers of osteoclasts as compared to WT were higher in OA mutant mice, serum levels of C-telopeptide of type I collagen (CTX) and osteocalcin, biomarkers for bone resorption and bone formation respectively, were significantly decreased. These data suggested that in mice the presence of truncated OA protein results in increased osteoclast number, but that they are inefficient in resorbing bone and may in part contribute to the increase in bone volume in OA mutant mice in vivo. To further investigate the role of OA in osteoclast differentiation, osteoclasts were differentiated from hematopoietic stem cell progenitors ex vivo. HSCs were cultured in the presence of 50 ng/ml of M-CSF for two days and then with M-CSF and 100 ng/ml of RANKL in the presence or absence of 50 ng/ml recombinant OA. We observed a dramatic increase in multinucleated TRAP-positive osteoclasts and the number of nuclei per osteoclast in OA-treated cultures compared to control. Additionally, analysis of HSCs showed increased cell proliferation in response to exogenous OA treatment. When osteoclasts were differentiated in ex vivo cultures derived from OA mutant and WT mice, we observed decreased osteoclast number, size, and function in OA mutant compared to WT cultures. This decrease was abrogated when cultures were treated exogenously with recombinant OA. Quantitative PCR analysis of RNA isolated during osteoclast differentiation from WT and OA mutant mice reveal decreased gene expression of critical osteoclast differentiation and functional markers, which explains the osteoclast defect observed ex vivo. To investigate the role of OA in osteoblast differentiation, primary osteoblasts were derived from mesenchymal progenitors isolated from calvariae of WT and OA mutant neonatal pups. OA mutant osteoblasts were found to have decreased alkaline phosphatase (ALP) staining and activity at day 14 in culture. Furthermore when cultures were differentiated to 21 days to simulate matrix mineralization in vitro, OA mutant osteoblasts exhibited decreased Alizarin Red and Von Kossa staining. Quantitative measurement of calcium also showed decreased mineral deposition in OA mutant mice compared to WT. Electron microscopic and protein studies were able to eliminate the notion of ER stress or cell toxicity as a result of ER stress playing a role in the delayed osteoblast differentiation observed in OA mutant osteoblasts. Furthermore, OA mutant osteoblasts exhibited decreased proliferation and survival ex vivo. These data reveal an effect of osteoactivin in osteoblasts ex vivo. This study provided an in vivo tool to study the role of osteoactivin in bone cells and the regulation of bone formation and bone resorption by this molecule. Taken together, these findings suggest that the presence of truncated OA leads to increased bone volume due to defective interplay between bone-resorbing osteoclasts and bone-forming osteoblasts. Data presented here support the notion of osteoactivin as a novel molecule in modulating skeletal homeostasis in vivo.
Temple University--Theses
Kim, Jaeyeon. "Model Analysis of Adipose Tissue and Whole Body Metabolism In Vivo". Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1216436630.
Jeitany, Maya. "Les mécanismes ALTernatifs de maintenance des télomères dans les cellules souches de gliome". Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T010/document.
Glioma stem cells (GSC), a subpopulation of tumor cells, are partly responsible for the failure of treatment of gliomas because of their resistance and regenerative capacity. The mechanism of alternative lengthening of telomere (ALT), based on homologous recombination, is detected in approximately 30 % of human gliomas. Therefore, therapeutic strategies directed specifically against ALT may have a therapeutic value. In this work, we further characterized the first model of human ALT GSC, the TG20 cells. We showed that despite their very high rate of recombination, the telomeres were still capable of fulfilling their protective function of chromosomes. We verified that the TG20 cells retained their ability to generate intracerebral tumors after serial transplantations in immunocompromised mice, while preserving an ALT phenotype. These results confirm the cancer stem properties of TG20 cells and the ability of ALT to ensure telomeres maintenance, which is required for the self-renewal and the high proliferation rate of GSC in vivo. Intracerebral grafts of TG20 cells in immunocompromised mice represent thus a good preclinical model for studying ALT gliomas. We have shown that treatment with a ligand of telomeric G-quadruplexes, the 360B, at an early stage of TG20 tumor engraftment, was able to inhibit tumor growth, showing the interest of the use of G-quadruplex ligands to specifically target ALT GSC. Transcriptomic profiling of TG20 cells and several other GSC telomerase-positive lines, incited us to study the roles of two homologous lysine acetyl transferases, PCAF (p300/CBP Associated Factor) and GCN5 (General Control Nonderepressible 5), in the regulation of telomeric recombination in ALT cells. We showed that the inhibition of these two proteins has opposite effects on the ALT mechanism. We propose that a balance of expression of PCAF and GCN5 regulates the telomere maintenance in ALT cells by controlling the turnover of TRF1. This model could serve for the development of new therapeutic strategies targeting ALT gliomas
Jarjour, Meryem. "Plasticité des réseaux de cellules folliculaires dentritiques : Développement & remodelage". Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4014.
Follicular Dendritic Cells (FDCs) regulate B cell function and development of high affinity antibody responses but little is known about their biology. FDCs associate in intricate cellular networks within secondary lymphoid organs. In vitro and ex vivo methods may thus be of little interest to understand the genuine immunobiology of FDCs in their native habitat. Herein, we utilised various multicolor fate mapping systems to investigate the ontogeny and dynamics of lymph node (LN) FDCs in situ. We show that LN FDC networks arise from the clonal expansion and differentiation of Marginal Reticular Cells (MRCs), a population of lymphoid stromal cells lining the LN subcapsular sinus. We further demonstrate that during an immune response, FDCs accumulate in germinal centers and that neither the recruitment of circulating progenitors nor the division of local mature FDCs significantly contributes to this accumulation. In contrast, we provide evidence that newly generated FDCs also arise from the proliferation and differentiation of MRCs, thus unraveling a critical function of this poorly defined stromal cell population
Chang, Cynthia J. "In vivo and in vitro models of distraction osteogenesis". Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558214.
Calabro, Lorenzo. "Improving in vivo models of fracture fixation associated osteomyelitis". Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/64112/1/Lorenzo_Calabro_Thesis.pdf.
Robin, Catherine. "Identification chez l'homme de cellules souches totipotentes lympho-myeloides transplantables in vivo dans un modele nod-scid". Paris 7, 2000. http://www.theses.fr/2000PA077205.
DAVID, PASCALE. "Transplantation d'hepatocytes isoles : de la disponibilite en cellules humaines a l'application dans un modele rat in vivo". Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13109.
PILLAI, Vinoshene. "Intravital two photon clcium imaging of glioblastoma mouse models". Doctoral thesis, Scuola Normale Superiore, 2021. http://hdl.handle.net/11384/109211.
Legaz, Sophie. "Les nanoparticules de poly(acide lactique) comme plateforme d'imagerie et de vectorisation de molécules actives chez Drosophila Melanogaster : analyses in cellulo et in vivo du couple GAL4/UAS". Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10293.
The biodegradable NanoParticles (NPs) of PolyLactic Acid) (PLA) are promising vectors for vaccination and therapeutic delivery. However, their in vivo evaluation is not always successful. NPs being undetectable in deep tissues, one of the challenges is the difficulty to follow the cellular uptake of these nanomaterials at the organism level. The aim of this thesis is to validate the use of PLA NPs as an imaging and drug vectorization platform in Drosophila melanogaster, and to analyze their fate in the whole fly body. The Drosophila model was chosen for its small footprint, the ease of breeding, the variety of transgenic lines, and the power of genetic tools available. Tt also allows to carry out in vivo mechanistic studies in a limited time window. We evaluated in cellulo and in vivo toxicity of these NP to determine optimal experimental conditions. Then the potential of PLA NPs was evaluated in cellulo on transiently transfected Drosophila cells by a plasmid carrying the GFP gene under the control of the UAS promoter. A simple observation by fluorescence microscopy of NPs vectorizing the gal4 gene or the GAL4 protein can confirm the effective delivery of active molecules into the cell through the binding of GAL4 protein to the UAS promoter. Finally, these formulations were orally administered to transgenic Drosophila UAS-RFP to confirm the previous in vivo results. GAL4 is a promising tool for indirect monitoring of NPs in transgenic organisms
Fenton, Mark. "The role of ageing in atherogenesis : two in vivo models". Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445443/.
Ölschläger, Peter. "In vitro and in silico models for in vivo events". [S.l. : s.n.], 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10252229.
MILANI, CHIARA. "Air pollution in neurodegeneration: in-vitro and in-vivo models". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/158159.
Particulate matter (PM) is a complex mixture of solid and liquid particles suspended in the air, and this suspension could be formed by a variety of particles of different size and composition depending on their origin (Marconi, 2003). Among the different fractions, ultrafine particles (UFPs) are thought to have the greatest health effects because of their characteristics. UFPs derive primarily from combustion processes in urban settings (Cassee et al., 2013) and, in the Lombardy Region, solid biomass burning (BC) for residential heating and diesel (DEP) combustion used for private and public transport represent their major sources (Longhin et al., 2016). Interestingly, emerging evidences from different studies suggest that neurological diseases, such as AD, PD and stroke, may be strongly associated with ambient PM (Genc at al., 2012). It has been demonstrated that continuous exposure to significant levels of airborne PM may result in the direct translocation of pollutants to different extra pulmonary sites, including central nervous system (CNS), or trigger the release of soluble inflammatory mediators from primary entry organs or secondary deposition sites (Genc at al., 2012). Systemic inflammation could activate cerebral endothelial cells, alter BBB integrity, or trigger signalling cascades that lead to the activation of MAPK and NFκB pathways (Calderón-Garcidueñas et al., 2008). Notably, post-mortem examinations of adult humans resident in highly polluted urban areas exhibited significantly higher brain COX-2 expression and accumulation of Aβ42 when compared to subjects living in cities with low pollution levels (Calderón-Garcidueñas et al., 2004). Therefore, the aim of this project was to evaluate the detrimental effect of UFPs exposure, regarding oxidative stress and inflammation, on in-vitro and in-vivo models of CNS. Moreover, this work meant to investigate the possible physiopathological correlation between these two mechanisms and AD neurodegeneration. First, we tested the effect of DEP administration on C6 glioma cells, which have properties of both astrocytes and oligodendrocytes. In fact, glial cells are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity (Lee and MacLean, 2015), and astrocytes have been recently linked to neuroinflammatory and neurotoxic pathways induced by PM exposure (Li et al., 2016). We demonstrated that DEP treatment at sub-lethal concentrations induced oxidative stress in glial cells, while inflammation was not involved. Moreover, we found that C6 glioma cells activate anti-oxidant pathways to contrast the oxidative status induced by DEP treatment and that the MEK-ERK1-2 pathway seems important in regulating these anti-oxidant strategies. Afterwards, we selected HT22 nerve cell line as a neuronal in-vitro model to study the effect of direct DEP administration. We demonstrated that DEP treatment at sub-lethal concentrations induced oxidative stress and inflammation in neuronal cells, supporting the idea that neurons are more sensitive to DEP administration than glial cells. Moreover, we extended the analysis of DEP detrimental effects and we found lipid reshaping and alteration of APP and BACE1 protein levels in HT22 cells. Finally, we exposed male BALB/c mice to single and repeated Intratracheal instillation of BC and DEP by means of a MicroSprayer® Aerosolizer system. This analysis confirmed the inflammatory and oxidative potential of BC and DEP exposure on mouse brain, which was accompanied by induction of PAHs metabolism and alteration of APP processing after sub-acute exposure. In conclusion, these findings may contribute to the knowledge of the interplay between PM exposure, the chronic oxidative stress and inflammation generation and the development of neurodegenerative diseases.
Lesnicar-Pucko, Gaja 1981. "Cellular mechanisms behind vertebrate limp outgrowth". Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/346928.
En aquest projecte utilitzem una nova tècnica de microscòpia in vivo, així com l’anàlisi del comportament cel.lular per tal d’investigar les bases cel.lulars de l’elongació de l’extremitat durant el desenvolupament embrionari. Investigacions recents clarament indiquen que activitats cel.lulars orientades estan involucrades en aquest procès, i d’entre elles la migració cel.lular i la divisió cel.lular orientada semblen les candidates més probables. Aquí presentem un estudi exhaustiu enfocat principalment en l’orientació cel.lular i el comportament cel.lular actiu durant el desenvolupament de l’extremitat del pollet. Trobem que les cel.lules s’orienten cap a l’ectodermi més proper i es divideixen al llarg a l’axis més llarg, així com veiem que, malgrat que el moviment cel.lular global mostra una tendència distal, la migració activa de cel.lules individuals sembla ser aleatòria. Donat que els nostres resultats no recolzen la teoria d’una migració distalment orientada amb divisió cel.lular orientada, proposem la intercal.lació cel.lular com al comportament cel.lular més probable involucrat en la morfogènesi de l’extremitat. Aquesta nova hipòtesi es veu validada mitjançant un model computacional de Cellular Potts que confirma el nostre supòsit
Rowland, Jennifer Elizabeth. "Analysis of growth hormone receptor signalling in vivo - transgenic mouse models /". [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17013.pdf.
Leoni, Francesca. "Hsp72 translocation and secretion in in vivo and in vitro models". Thesis, University of Chester, 2009. http://hdl.handle.net/10034/93835.
Thangavelu, Amudha. "Targeted therapies in endomental cancer - in vitro and in vivo models". Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531515.
Aston, Nicola Susan. "In vivo and in vitro models for infantile copper-associated cirrhosis". Thesis, University of Sheffield, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264442.
Zwaini, Zinah Dheyaa Razzaq. "In vitro and in vivo models of renal ischemia reperfusion injury". Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/39344.
Shahidipour, H. "Development of in vitro and in vivo models of uveal melanoma". Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3004584/.
Culver, Hannah. "Modulation of leukocyte recruitment in animal models of inflammation in vivo". Thesis, Griffith University, 2009. http://hdl.handle.net/10072/365779.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text
Angioi, Duprez Karine. "Le melanome malin oculaire et le retinoblastome : deux modeles d'etudes cliniques et experimentales in vivo de la proliferation cancereuse humaine ; a propos de 12 observations". Nancy 1, 1991. http://www.theses.fr/1991NAN11189.
Joly, Candie. "Dynamique des réponses lymphocytaires T locales et systémiques à l'injection d'un vaccin dans la peau". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS317.
Vaccination has been considered as one of the greatest discoveries in the history of infectious diseases by allowing pathogens decline or eradication. However, we still ignore all the mechanism that lead to protection and therefore, fail to elaborate new vaccines against HIV, tuberculosis, malaria and emergent pathogens. Recently, efforts have been made to elicit effective cellular response after vaccination, which is crucial for pathogen clearance.This thesis relied on live-attenuated vaccine model derived from the vaccinia virus: the MVA (Modified Vaccinia Ankara) and a non-human primate model. We characterized the cellular immune response triggered by a homologous prime-boost intradermal injection of MVA, with a 2 months and 9 months boost. The MVA induced a massive infiltration of CD8 T cells at the injection site 7 days post immunization. In comparison, the systemic cellular response was mild and did not reflect the magnitude of the local response. The prime and boost injections elicited distinct orientation of the systemic and local T cells, which led to an important induction of a persistent, antigen-specific and polyfunctional CD8 and CD4 T cell responses after the 9 months boost.This work emphasizes the difference between local and systemic response, demonstrating the importance of the focus on tissue immunity. It also highlights the impact of the immunization schedule on the quality of the cellular response
Hooley, Robert P. "Studies on Sertoli cell function using in vivo and in vitro models". Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/24705.
McDonald, Lita E. C. "The establishment of in vivo and in vitro models for myoclonus dystonia". Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27889.
Kalber, Tammy Louise. "In vivo susceptibility-contrast MRI studies of mouse models of liver metastasis". Thesis, St George's, University of London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440446.
Emerson, Michael. "Endogenous nitric oxide and platelet function in in vivo models of thromboembolism". Thesis, King's College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300152.
Immonen, Taina Tuulia. "Computational Models of Ex Vivo HIV-1 Dynamics and Fitness Across Scales". Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1365173809.
Ahmed, Jamileh. "Receptor-Associated Protein (RAP) Models In Vivo Reelin Haploinsufficiency: Implications in Schizophrenia". Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6670.
Lattanzio, Francesca <1982>. "Biomolecular studies in Alzheimer’s Disease models: investigations in vitro and in vivo". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5507/1/Lattanzio_Francesca_tesi.pdf.
Lattanzio, Francesca <1982>. "Biomolecular studies in Alzheimer’s Disease models: investigations in vitro and in vivo". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5507/.
Renaud, Matthieu. "Évaluation d'un substitut osseux résorbable porteur de cellules souches : approche cellulaire pour la régénération osseuse in vivo". Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT081.
Despite the development of biomaterials in the field of bone grafts and alveolar preservation, the results are no sufficient to made reconstructions ad integrum of bone tissue. Bone engineering techniques seem to be the preferred way to improve our surgical techniques. Porous silicon is a promising material for tissue engineering and especially for bone regeneration. Indeed, its surface allows cell adhesion. And then, it’s a non-toxic and bioresorbable interesting material properties carrying stem cells. Dental pulp stem cells (DPSC) are easily accessible cells in the oral cavity. Their proliferation and differentiation capacities associated with porous silicon appear to be attractive for therapeutic applications in bone regeneration. The results of the in vitro studies have shown the interest for in vivo application. In this thesis, we have tested the combination of porous silicon and dental pulp stem cells in vivo experimentation, using the same characteristics of the in vitro reference study. For this, the material was produced in particle form to be used as bone filling material, associated or not with DPSC. The rat-tail model was developed and tested to reduce the number of animals needed for the study while maintaining the statistical power of the results. Studies have shown the possibility of using this model for bone regeneration defects surgically created. In addition, it seems that this model can also be useful for studies on osseointegration of implantable systems and bone regeneration around these implants. Then, the porous silicon was tested under these conditions, with or without DPSC, in comparison with a positive control and a negative control. This association has emerged as a promising approach for bone regeneration in vivo
Wall, Lucy Rosalind. "The proliferative activity of interferon on ovarian cancer : in vitro and vivo models". Thesis, Queen Mary, University of London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398948.
Ljungdahl, Ståhle Ewa. "In vivo and in vitro models for determination of antiviral activity and resistance /". Stockholm, 1997. http://www.kibic.ki.se/ki/diss/971212ljun.html.
Griffin, Michael. "Use of in vitro metabolism models for in vivo drug metabolic clearance prediction". Thesis, University of Manchester, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487998.
Pugh, Perdita Lucy. "Development of rodent in vivo models : neuroinflammation and neurodegeneration relevant to Alzheimer's disease". Thesis, Cardiff University, 2007. http://orca.cf.ac.uk/56148/.