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Mechanisms by which cell surface engineering of the endothelial glycocalyx with a sialic acid-containing polymer prevents organ transplant rejection

Resource type
Thesis type
(Thesis) M.Sc.
Date created
2024-02-16
Authors/Contributors
Abstract
Organ transplant rejection is prevented by immunosuppressants, but these drugs do not always work and are associated with many side effects. To circumvent the use of these immunosuppressants, a cell surface engineering (CSE) approach that enzymatically adheres a sialic acid-containing polymer, LPG-Sia, to endothelial cells in blood vessels prior to transplantation was developed. I investigated the mechanisms by which this protocol inhibits immune cell activation. Co-culture assays showed that LPG-Sia decreased immune-mediated endothelial cell death. Blocking sialic acid receptors, siglec-7 and -9, prevented the protective effect of LPG-Sia indicating that they were required for immune inhibition. Transplantation of CSE modified allogeneic arteries reduced co-stimulatory molecule CD86 expression on recipient conventional dendritic cells. Also, accumulation of macrophages, CD4 and CD8 T cells were reduced in CSE modified allograft arteries. Together, these findings indicate that LPG-Sia deactivates immune cells by acting on siglec-7 and -9, and that it reduces early activation of antigen presenting cells that may prevent T cell activation and resultant rejection.
Document
Extent
59 pages.
Identifier
etd22955
Copyright statement
Copyright is held by the author(s).
Permissions
This thesis may be printed or downloaded for non-commercial research and scholarly purposes.
Supervisor or Senior Supervisor
Thesis advisor: Choy, Jonathan
Language
English
Download file Size
etd22955.pdf 3.33 MB

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