ORCID
https://orcid.org/ 0000-0003-0232-1783
Date of Award
Spring 5-20-2022
Degree Name
Master of Science (MS)
Degree Type
Thesis
Abstract
Alzheimer’s disease is the most common cause of dementia. None of the available drugs can cure the disease. Chimeric Antigen Receptor (CAR) macrophages, because of their phagocytic activity, have potential as a cellular treatment for amyloid aggregation. In this study, we generated an anti-amyloid CAR hematopoietic progenitor cell line. By inducing the progenitor cell line to differentiate into macrophages, we show that the anti-amyloid CAR-Macrophage has enhanced specific phagocytic activity towards amyloid in in vitro experiments. In addition, in ex vivo experiments, anti-amyloid CAR significantly reduces the plaque load on brain slice from APP/PS1 mice when compared to a non-targeted CAR. We then transduce the progenitor cell line with GFP-luciferase and found that transduction of GFP-luciferase did not have a significant effect on the phagocytosis of amyloid. By tracking the luciferase activity in brain, we found that these CAR-macrophages can live for more than 10 days after intracranial injection.
Language
English (en)
Chair
Dr. Carl DeSelm
Committee Members
Dr. Michael Vahey Dr. Abhinav Diwan Dr. Hong Chen