Development of Specifically Ablatable Neural Precursor Cells to Investigate the Cell-Based Mechanism of Exogenous Cell Transplants
Year: 2018
Type: dissertation
Abstract: Stroke is a leading cause of long-term disability, and new therapies are needed to improve quality of life for those affected. Stem cell transplantation produces functional recovery in rodent stroke models, but therapeutic mechanisms remain unclear. Transplanted neural precursor cells (NPCs) lead to functional recovery in rodents following stroke and differentiate into neural cell types; whether they need to integrate into host tissue long-term to be therapeutic remains to be elucidated. To study this, I have engineered specifically ablatable cortical neuroepithelial cells (cNEPs), allowing transplant ablation to determine whether cells are required for long-term functional recovery. Engineered cNEPs express nitroreductase, allowing conversion of metronidazole (MTZ) into toxic metabolites, and respond to MTZ in a dose response manner, allowing ablation in vitro/in vivo with no bystander effect between 100μg/ml - 400μg/ml of MTZ. Transplanted into rodents, these cells enable study of mechanisms of functional recovery mediated by NPC transplants.
Source: TSpace (University of Toronto)
Author: Stasja Drecun
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3152655685