Immune modulation with amniotic epithelial cells in pancreatic islet transplantation

Qureshi, Khalid (2012). Immune modulation with amniotic epithelial cells in pancreatic islet transplantation. University of Birmingham. M.D.

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Abstract

Chronic systemic immunosuppression in pancreatic islet transplantation restricts its clinical application. This study aims to explore the potential of cell-mediated immune-modulation as an alternative to conventional immunosuppressive regimens; specifically investigating the innate immunosuppressive properties of human amniotic epithelial cells (AEC). Cell constructs composed of human islets and AEC (islet:AEC) were bio-engineered in rotational culture. Insulin secretory capacity and immuno-modulatory potential were characterised using appropriate in vitro assays. Fluorescence immunocytochemistry and multiplex arrays was used to identify putative mediators of the immunosuppressive response in isolated AEC monocultures. Islets and islet:AEC constructs demonstrated sustained, physiologically-appropriate insulin secretion. Resting peripheral blood mononuclear cells (PBMC) were activated on exposure to human islets but this response was significantly (p<0.05) attenuated in islet:AEC constructs. Phytohaemagglutinin (5\( \mu \)g/ml)-induced PBMC proliferation was sustained on contact with unmodified islets but abrogated in AEC and islet:AEC constructs. CD4+ and CD8+ T-cell proliferation was responsive to AEC; their in vitro expansion both in response to CD3/CD28 activation and contact with human islets being suppressed by the presence of AEC. Transplanted islets may thus benefit from an immune-privilege status conferred on them as a consequence of their close proximity to human AEC. Such an approach may diminish the requirement for generalised systemic immunosuppression in islet transplantation.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

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