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Thesis
Validating cerebral organoids as a model for the effects of HIV-1 on astrocytic cytokine expression
Master of Science (M.S.), Drexel University
Feb 2026
DOI:
https://doi.org/10.17918/00011324
Abstract
Reactive astrocytes and neuroinflammation have long been indicated in the development of HIV associated neurocognitive disorders (HAND). Elucidating the biochemical and functional changes HIV-1 has on cells in the CNS, as well as the altered mechanisms that contribute to HAND development has been difficult to study in cellular and animal models. Therefore, we attempted to validate the recapitulation ability of cerebral organoids (COs) innate immune function when infected with HIV-1. After development of COs from induced pluripotent stem cells, we showed a small percentage of astrocytes (2%) along with a large population of neurons forming in recently mature COs. We then characterized cell types by examining 15 different markers of pluripotency and cell differentiation. Next, we infected COs with HIV BaL-GFP and HIV ADA and examined HIV-1's effect on the ratio of gene expression in those same 15 markers. We mostly observed a decrease in expression after HIV-1 infection, except in astrocyte markers GFAP and ALDH1L1 which increased in expression when infected with HIV-1. Finally, we compared proinflammatory cytokine expression over time between 3 organoids and one human brain slice (HBS) case when infected with HIV-1. We observed the ability of the cerebral organoids to produce proinflammatory cytokines in response to infection, as well as a peak in cytokine expression matching with the peak of infection determined by AlphaLISA. We believe these findings collectively show that cerebral organoids are an advantageous model to further study astrocyte reactivity and mechanisms of neuroinflammation pertaining to HIV-1 infection in the CNS.
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Details
- Title
- Validating cerebral organoids as a model for the effects of HIV-1 on astrocytic cytokine expression
- Creators
- Isabella Bendorf
- Contributors
- Zachary Klase (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University
- Number of pages
- 87 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991022170151204721