3D Bioprinting Patient-Derived Induced Pluripotent Stem Cell Models of Alzheimer’s Disease using Drug Releasing Microspheres
| dc.contributor.author | Benwood, Claire | |
| dc.contributor.supervisor | Willerth, Stephanie | |
| dc.date.accessioned | 2022-09-27T17:09:51Z | |
| dc.date.available | 2022-09-27T17:09:51Z | |
| dc.date.copyright | 2022 | en_US |
| dc.date.issued | 2022-09-27 | |
| dc.degree.department | Department of Mechanical Engineering | |
| dc.degree.level | Master of Applied Science M.A.Sc. | en_US |
| dc.description.abstract | Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is becoming increasingly prevalent in aging populations. It is characterized by the buildup of amyloid beta plaques and neurofibrillary tangles containing hyperphosphorylated-tau. The current treatments for AD are only symptomatic and do not prevent the long-term progression of the disease. Basal forebrain cholinergic neurons (BFCNs), responsible for memory and spatial learning, are the first to be affected and degenerate in AD. Microspheres are small spherical particles that can release their encapsulated drugs at a controlled rate. Their ability to release drugs slowly over a long period of time is beneficial when differentiating human induced pluripotent stem cells (hiPSCs) into neural progenitor cells (NPCs) and more specialized neurons. Here, I differentiated patient derived hiPSCs into NPCs and used the Aspect RX1 microfluidic printer to produce dome-shaped constructs. The combination of cells, bioink that mimics the extracellular matrix (ECM), and purmorphamine (puro) releasing microspheres directs the differentiation of NPCs into BFCNs. These AD tissue models were then characterized with cell viability, immunocytochemistry, and electrophysiology to evaluate their functionality and physiology for use as disease-specific neural models. The neuronal and cholinergic markers Tuj1, FOXG1, and ChAT were identified as well as the Alzheimer markers Amyloid beta and tau. Further, immature electrical activity was observed when the cells were excited with potassium chloride (KCl) and acetylcholine (ACh).These tissue neural tissue constructs show potential for the use of patient-specific drug screening as well as a model to increase understanding about the progression of AD. | en_US |
| dc.description.scholarlevel | Graduate | en_US |
| dc.identifier.uri | http://hdl.handle.net/1828/14269 | |
| dc.language | English | eng |
| dc.language.iso | en | en_US |
| dc.rights | Available to the World Wide Web | en_US |
| dc.title | 3D Bioprinting Patient-Derived Induced Pluripotent Stem Cell Models of Alzheimer’s Disease using Drug Releasing Microspheres | en_US |
| dc.type | Thesis | en_US |