Acute cellular responses to oxygen-glucose deprivation/reperfusion in human induced pluripotent stem cell-derived neurons

Sedighipour Chafjiri, Marzieh (2025) Acute cellular responses to oxygen-glucose deprivation/reperfusion in human induced pluripotent stem cell-derived neurons. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (9MB)

Abstract

Ischemic stroke occurs when a blood clot obstructs blood flow to the brain, depriving brain cells of oxygen and glucose and causing cell death. In the acute post-stroke period, the ischemic core can expand into the penumbra due to delayed death of injured neurons. There are no treatments in the clinic that specifically rescue these injured neurons. Although strategies to rescue injured neurons have proven effective in preclinical studies, they have failed to translate into clinical treatments due to a combination of factors including species differences. The development of human-induced pluripotent stem cells (hiPSCs) has provided an opportunity to study how human neurons respond to ischemia in real-time. The goal of this project was to establish a cell culture model of hiPSC-derived neurons and assess the cellular response to an ischemic insult. After 2 weeks, hiPSC cultures consisted primarily of neural progenitor cells (NPCs) and neurons. To replicate ischemic conditions of the penumbra, oxygen-glucose-deprivation/reperfusion (OGD/R) was used. Apoptosis significantly increased at 24h post-OGD. Neurons were more susceptible to OGD/R compared to NPCs, exhibiting greater cell death. This study has provided an in vitro model for understanding the cellular mechanisms post-stroke, potentially bridging the gap between preclinical findings and clinical treatments.

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