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Title: Maternal microchimerism in type 1 diabetes
Author: Ye, Yi Jody
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Maternal microchimerism (MMc) results from transfer of maternal cells to the fetus during pregnancy. These cells persist into adulthood in peripheral blood as well as multiple parenchymal organs and high levels of MMc have been associated with Type 1 diabetes mellitus (TID). To understand the potential importance of MMc in T1D the aims of this PhD were 1. to develop strategies to detect and phenotype MMc in healthy human pancreas 2. to compare MMc frequency and phenotype in healthy and T1D pancreas 3. to develop strategies to confirm the 'maternal ' origin of MMc at the molecular level MMc positive for markers of fully differentiated endocrine, acinar, and ductal cells were identified in healthy human pancreas. The frequencies of insulin+ MMc varied from 0.05% to 0.8%. Some MMc in neonatal pancreas were positive for Ki67, indicating their potential for replication. MMc were detected in fresh islets, as well as in islet-derived cells. In male T1D pancreas, no female CD45+ cells were observed in insulitis, indicating that MMc are not effector cells of the autoimmune response. Laser capture microdissection of FISH-labelled candidate cells from frozen sections was successful. FISH did not interfere with the subsequent genotyping. PCR efficiencics of pooled cells (10) vs. single cells were 100% vs. 23.1%. Additionally, a separate aim of this project was to determine whether adult human islets were amenable to immortalisation using an SV40lhTERT retroviral system and characterisation of an islet derived cell line is described. These studies indicate that some maternal cells have multilineage potential. Increased levels of MMc in TlD may represent a failure of anti-maternal tolerance or contribute to attempted tissue repair but they do not facilitate host beta cell attack. Further studies are required using the strategies developed in this study to better define the role of MMc in T1D.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available