Encapsulation of pancreatic beta cells

Nikravesh, Niusha (2017). Encapsulation of pancreatic beta cells. University of Birmingham. Ph.D.

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Abstract

Immunoisolation of pancreatic beta cells is a promising approach for the treatment of type I diabetes. In this thesis, a vibrating nozzle technology was utilised to reproducibly generate 1% alginate microparticles with an average diameter of 200 μm±19 S.D. This technology further enabled the application of fluidised bed bioreactor owing to high uniformity of particles, an important parameter for achieving homogeneous fluidisation. Experimental data collected from the cultivation of cells in fluidised culture was shown to provide a promising solution for handling encapsulated cells from manufacturing phase to clinical sites, which is currently a challenging issue for cell-based therapies. A reduction in beta cells insulin-secreting ability was observed after two weeks of static culture. This problem was addressed by investigating a 3- dimentional culturing technique and a novel polyelectrolyte multilayer (PEM) coating approach. Concave agarose micro-wells were used to culture robust pancreatic beta cell spheroids that enhanced cell-cell contact. Additionally, the novel PEM coating using Ca2+ pre- conditioning improved cell function while providing immunoisolation from cytokines, and reducing the total volume of the graft. This work presented an effective immunoisolation and culturing system to improve cells survival rate, which hopes to bring a closer step towards therapeutic transplantation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):