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|Title:||STUDY OF SPECIES SPECIFIC IMMUNITY BY DEVELOPING CHIMERIC ANIMAL MODELS||Authors:||YONG SU MEI KYLIE||ORCID iD:||orcid.org/0000-0001-9118-7584||Keywords:||Chimeric mouse, Hematopoietic cell expansion, Hematopoietic cell transplantation, Humanised mice, Biologic testing, Immunotoxicity||Issue Date:||12-Jan-2018||Citation:||YONG SU MEI KYLIE (2018-01-12). STUDY OF SPECIES SPECIFIC IMMUNITY BY DEVELOPING CHIMERIC ANIMAL MODELS. ScholarBank@NUS Repository.||Abstract:||In this dissertation, we present the importance of establishing chimeric animal models (humanised mouse and bat-mouse model) for the study of species-specific immune responses which are difficult to investigate within the species themselves. First, we identified a CD34loCD133lo cell population within the human fetal liver that expresses crucial growth factors which enables them to support ex vivo hematopoietic stem cell (HSC) expansion. These expanded HSCs were engrafted into an immunodeficient mouse strain NOD scid gamma (NSG), to create a larger number of animal models (humanised mice with human immune system) for the evaluation and comparison of known immunotoxic Biologics, Proleukin®/IL-2 and OKT3 to published clinical studies. Bats are another important species with ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproductive rates. By adopting the concept of chimeric humanised mice, we transplanted bat cells into NSG mice and successfully reconstituted bat immune cells in mice with unique features including resistance to graft rejection and functional antigen-specific bat antibody responses. The successful creation of these novel chimeric animal models provides powerful platforms for both basic and translational research on humans and bats.||URI:||http://scholarbank.nus.edu.sg/handle/10635/142202|
|Appears in Collections:||Ph.D Theses (Open)|
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