Saudi Cultural Missions Theses & Dissertations
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Item Restricted Subcellular Location-Dependent Regulation of Interferon-Induced Transmembrane Protein 1 in Glioblastoma(The University of Edinburgh, 2024) Mubarak, Rawan; Ball, KathrynGlioblastoma multiforme (GBM) is one of the most aggressive and lethal brain cancers, known for its highly invasive nature and resistance to conventional therapies. Central to this resistance is the presence of glioblastoma stem cells (GSCs), which contribute to tumour recurrence and heterogeneity. This thesis investigates the roles of interferon-induced transmembrane proteins (IFITMs), specifically IFITM1 and IFITM3, within GSCs and their potential as therapeutic targets. The study provides a detailed analysis of IFITM1’s expression, subcellular localisation, and interaction with other proteins in response to interferon stimulation, employing advanced molecular techniques such as co-immunoprecipitation, immunofluorescence microscopy, and proteomic analysis. Key findings include the discovery that IFITM3 plays a critical role in regulating IFITM1’s expression and localisation, with significant implications for IFITM1’s function in cancer cell biology. This thesis also contributes to validating a novel interaction between IFITM1 and Lysosomal-associated membrane protein 1, suggesting a potential role for IFITM1 in autophagy, which could be pivotal in GBM’s resistance to treatment. These insights not only advance the understanding of IFITM proteins in GSCs but also highlight their potential as targets for therapeutic intervention in GBM. This work lays the foundation for future studies aimed at manipulating IFITM proteins to develop novel strategies for overcoming GBM treatment resistance.42 0Item Restricted Investigating Amniotic Fluid Stem Cells Epithelial to Mesenchymal Transition in Culture(Saudi Digital Library, 2023-12-01) Qassem, Maha Abdulraheem; Gerli, Mattia; Beesley, MaxAmniotic fluid plays a vital role in supporting the growth and development of the fetus. Different research studies have found the AF to have significant potential in treating diseases through regenerative medicine and tissue engineering. AF has also been of detrimental importance in diagnosing chromosomal abnormalities and neural tube defects, for which it’s been used for the past 40 years. The composition of the fluid is highly heterogeneous and highlights the presence of various proteins, cell cells, and stem cells. The aim of this project is to understand the identity of the Amniotic Fluid-derived Mesenchymal Stem Cells and prove that these originated through an Epithelial-Mesenchymal transition (EMT) process, happening in cultures over different time points. Four amniotic-fluid samples were collected for this research. The physician collected the samples using an amnio-drainage procedure and the samples were cultured using standard protocols. Once the cultures are established, flow cytometry was used to provide accelerated analysis of individual cells. The results showed that the expression of mesenchymal markers such as CD73 and CD90 start to elevate upon culture on Day 7 and keep increasing during the time points. In opposition, the AF cells exhibit reduced epithelial markers expression, shown by decreased detection of EpCAM. E-Cad expression begins to recover and increase by Day 14. In conclusion, AF mesenchymal stem cells are not inherently present in the amniotic fluid but only exist in an epithelial state in vivo. AFSC produces more mesenchymal proteins as they are cultured, undergoing EMT. These findings have implications for using AF stem cells in regenerative medicine and would allow an improved understanding of their fetal origins.15 0Item Restricted INJECTION OF RAT MESENCHYMAL STEM CELLS LEADS TO HOMING AND DIFFERENTIATION IN THE LIVER IN A BLUNT LIVER TRAUMA MODEL(Saudi Digital Library, 2020-12-02) Alhabboubi, Mostafa; Razek, Tarek; Shum Tim, Dominique; Gao, Zu Ha; Khwaja, Kosar; Khwaja, KosarBackground: The liver heals remarkably after different forms of injuries. However, healing time can be lengthy following high-grade blunt injuries. We hypothesize that injected bone marrow derived mesenchymal stem cells (MSC) could locate and differentiate to hepatocytes after blunt trauma using a rat liver trauma model. Methods: Blunt liver trauma was induced to Lewis rats. MSC were extracted from Lewis rats’ femurs and transfected with LacZ retrovirus so that they express B- galactosidase enzyme, giving their nuclei a blue color on light microscopy. Each rat received a single dose of BMDS (n=6 x 106) within 24 hours of trauma. Through different steps of the experiment, route of injection was the tail vein (TV) in 9 rats, the portal vein (PV) in 19 rats and directly to the injured liver (DI) in 6 rats. Rats were euthanized at 2, 7 days after injection of MSC. Livers were harvested and examined under light microscopy to identify the MSC. Results: Liver sections showed localization and active migration of MSC to trauma sites in the PV group euthanized at 48 hours (3/10 rats). Furthermore, some stem cells differentiated to hepatocytes. Although with fewer cells, similar findings were present in 1/9 rats euthanized at 7 days in the PV group. There was no evidence of MSC localization in TV and DI groups. 4 Conclusions: MSC can locate and differentiate to hepatocytes at blunt trauma site and may contribute to liver regeneration process. Portal vein injection of MSC has emerged as the most effective method of delivery to the liver following trauma among different delivery methods studied. This technique has the potential to become an effective therapeutic strategy to improve liver regeneration after severe blunt trauma. Methods of optimizing homing to injured tissue and evaluation of differentiated stem cell functionality are future areas of research.3 0Item Restricted The Effect of Simvastatin Scaffolds on human Periodontal Ligament Cells as a Potential Endodontic Regenerative Technique(2023) Almohimeed, Khawlah; Crawford, Aileen; Martin, NicolasRegenerative endodontic procedures have received considerable critical attention in the field of restorative and paediatric dentistry. Vital pulp is the best filling material a tooth can have, thus, maintaining pulp vitality is crucial in this respect. This is a preliminary study is to investigate the dose and timely release of 2% simvastatin from PLGA scaffolds as well as assess viability of human periodontal ligament cells (hPDL). The release of simvastatin in DMEM was much higher than PBS in the first 24 hours. Due to limitations in accessing the lab during Covid-19 Pandemic, spectrophotometer readings have only been obtained for a 96-hour incubation period on the Simvastatin PLGA scaffolds. HPDL showed viability after 96-hour incubation in 2% simvastatin PLGA scaffolds. the conclusion was that our newly fabricated 2% simvastatin PLGA scaffolds showed biocompatibility. Within the limitations of this study, we can conclude that using the newly fabricated 2% simvastatin PLGA scaffolds-maintained cell viability for 96 hours although it was lower than desired. Further research is needed in this respect especially that the present study contains preliminary data.26 0