Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 30 for “"human iPSC"”.
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Modelling neurodegenerative diseases in human iPSC-derived neurons
… the derivation of in vitro disease models using human iPSC-derived neurons to provide a more accurate understanding of how disease mutations affect neuronal health. I first sought to model the polyglutamine disease spinal and bulbar muscular atrophy (SBMA), detailed in Chapter 4. Using iPSCs …
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Modeling colorectal cancer initiation using human iPSC-derived intestinal organoids
OBJECTIVE: Human induced pluripotent stem cell (hiPSC)-derived human intestinal organoids (HIOs) are increasingly utilized as in-vitro models for studying colorectal cancer (CRC). Prevalent oncogenic drivers in CRC include mutations in EGFR (L858R), KRAS (G12D) and CTNNB1 (S33C) which are known to …
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Phenotypic characterisation of human iPSC neuronal models of GM2 gangliosidoses
… a model of these diseases using an inducible, human stem cell-based neuronal cell line (i3N). This isogenic cellular system allows for rapid, large-scale growth of stem cell-derived cortical glutamatergic neurons, enabling experiments that require large amounts of input material such as mass …
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Investigating Parkinson’s Disease human iPSC-derived models through single-cell gene expression
… use in research, induced pluripotent stem cell(iPSC) technologies are still under active development for clinical and disease modeling purposes. Directed differentiation protocols of iPSC to midbrain dopaminergic neurons enables the study human midbrain Dopamine(DA) neurons, the primary neuronal …
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Development of Novel Therapies for Marfan Syndrome using a Human iPSC-disease model
… in the pathogenicity. Here, I use a patient iPSC-derived in vitro disease model that recapitulates the complexity of the patient abnormalities (Granata et al. 2017) to develop two potential therapeutic strategies (i) directly interfering at the level of the pathological mutation using an exon …
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Development of a High-Throughput Human iPSC Chondrogenesis Platform and Applications for Arthritis Disease Modeling
<p>The differentiation of human induced pluripotent stem cells (hiPSCs) to prescribed cell fates enables the engineering of patient-specific tissue types, such as hyaline cartilage, for applications in regenerative medicine, disease modeling, and drug screening. In many cases, however, these …
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Parkinson's Disease-Associated Protein VPS13C Regulates Phospho-Rab10-Mediated Lysosomal Function in Human iPSC-Derived Dopaminergic Neurons
… of VPS13C in Parkinson’s disease-relevant human dopaminergic neurons has not yet been investigated. This thesis established a PD-relevant model using human induced pluripotent stem cell-derived dopaminergic neurons and identified an important role for VPS13C in lysosomal homeostasis. …
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Genetic programming of human iPSC-derived macrophages provides a tool to study the Erythroblastic Island niche in vitro
… tissue function and disease. Studies involving human macrophages have been hampered due to the ethical constraints and technical difficulties related to their isolation/derivation for in vitro expansion, and to the difficulty of genetically modifying them to interrogate the role of specific …
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Using single-cell RNA-seq to assess the effect of common genetic variants on gene expression during development
… in development. The challenge of studying early human development is partially overcome by advances in stem cell technologies. In particular, induced pluripotent stem cells (iPSCs) and cells derived therefrom represent a fantastic system to study development in vitro. In this thesis, I …
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The interconnected roles of spastin and protrudin in endosomal sorting
… tubule fission in non-polarised cells and in human iPSC-derived neurons. This required protrudin’s ability to bind VAPA/B and endosomal PtdIns3P, as well as its coiled coil domain previously implicated in kinesin-1 interaction. Tug-of-war between kinesin and dynein microtubule motors has been …
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Investigating Induced Pluripotent Stem Cells for Tissue Engineering and Hepatotoxicity Applications
Induced pluripotent stem cells (iPSCs) can be differentiated into multiple cell types in the body while maintaining proliferative capabilities. The generation of human iPSC-derived hepatocytes (iPSC-Heps) has resulted in a new source for hepatic cells. The current available options for human …
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CONSEQUENCES OF CHROMATIN MOSAICISM AND PERSISTENCE IN NEURONAL PLASTICITY AND DISEASE
… architectures. In neuronal plasticity, using human iPSC-derived neurons, I describe how activity-dependent chromatin loops persist for at least five days following stimulation. Chromatin loops plasticity and persistent histone modification at regulatory elements are linked to persistent …
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A biohybrid bridge between brain and machine: Development and application of a neural implant using iPSC-derived neuronal membranes
… hypothesis that the use of material derived from human-derived neurons themselves as a biological mediator, incorporated in the device design, would result in reduced inflammation and improved therapeutic efficacy and stability *in vivo*. To test this hypothesis, the project fused flexible …
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Engineering Complex Kidney Structures for Disease Modelling, Drug Testing, and Studying Kidney Development
… Optimising the protocol and using different human iPSC lines, we successfully engineered functional human ureteric bud (UB)-like tubules capable of recapitulating early steps of UB morphogenesis. Exploiting these developmental capacities, we used tubules to identify a novel growth factor …
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Developing an induced pluripotent stem cell model of pulmonary arterial hypertension to understand the contribution of BMPR2 mutations to disease-associated phenotypes in smooth muscle cells
… of clinical disease. Furthermore, limited human tissue is available for study and usually only from patients with end-stage disease, making it difficult to understand how PAH is established and progresses. Alternative human models of PAH are therefore required. This thesis describes the …
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DISSECTING THE MOLECULAR MECHANISMS RELATED TO THE ONSET OF NEUROLOGICAL COMPLICATIONS IN THREE CELLULAR MODELS OF SARS-COV 2 INFECTION: IPSC-DERIVED MOTO R NEURONS, IPSC-DERIVED DOPAMINERGIC NEURONS, IPSC DERIVED-HUMAN CORTICAL ORGANOIDS.
… of success [29–37]. Further, considering that human brain tissue is difficult to access, particularly from patients with a contagious pathogen due to safety concerns [38], 2D and 3D in vitro models can provide a viable and safe alternative and represent a suitable model system to test the …
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Lysosomes and Ribonucleoprotein Dynamics in Neurons
… we developed methods to engineer and culture human iPSC-derived neurons. Within this system, we used proximity labeling proteomics to profile the lysosomal surface proteome. We discovered that annexin A11 (ANXA11), a protein linked to familial amyotrophic lateral sclerosis (ALS), is a novel …
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Effect of Parkinson’s disease-related alpha-synuclein abnormalities on the maturation of distinct iPSC-derived neuronal populations
… them into induced pluripotent stem cells (iPSCs), and differentiating iPSCs into neurons. For this project, iPSCs derived from two PD patients, one harbouring the A53T SNCA mutation, the other a SNCA triplication, and three healthy individuals, were employed. In the initial stage, I …
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Biohybrid Peripheral Neural Interfaces: Combining Cell Transplantation and Flexible Electronics for Functional Neurological Restoration
… with that of native nerve. The device hosts iPSC derived myocytes on the electrically active surface, allowing their efficient electrical recording. I have shown survival of human iPSC derived muscle in a rat for up to seven days post implantation in a rat model. I have developed a strong …
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