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New strategies to support cell survival post- transplantation for the treatment of Parkinson’s Disease

Hakami, Abrar 2024. New strategies to support cell survival post- transplantation for the treatment of Parkinson’s Disease. PhD Thesis, Cardiff University.
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Cell therapies hold the potential to significantly reduce the debilitating effect of several neurodegenerative diseases, including Parkinson’s Disease (PD). Despite showing promise, one of the primary drawbacks is cell death after transplantation. This work aimed to explore new approaches using biomaterial-based systems to support the survival of transplanted cells after transplantation. One class of biomaterials called cryogels has been shown to possess several distinct advantages over conventional biomaterials. They are characterized by interconnected macroporous networks that not only allow fluid transport throughout their structure but also create a high surface area to volume ratio for cell growth or protein loading. In this work, the cryogels were synthesized from synthetic monomers containing poly (ethylene glycol) diacrylate (PEGDA) and either 3-sulfopropyl acrylate (SPA) or 2- (dimethylamino)ethyl methacrylate (DMAEMA), which introduced a negative and positive charge into cryogels network, respectively. Cryogel microcarriers were successfully developed using microfluidic devices to generate water-in-oil emulsion (as a template) followed by the cryogelation process. Firstly, SPA cryogel microcarriers aimed to control the release of growth factors (GDNF and BDNF), which play an important role in regulating the growth and survival of neurons, through electrostatic interactions. GDNF and BDNF showed different loading percentages into cryogels with different release profiles depending on the SPA (negative charge) amount. Moreover, biological studies confirmed the biocompatibility of cryogels and their ability to deliver GDNF and BDNF into the healthy rat brain. Secondly, DMAEMA cryogel microcarriers were utilized as another approach to improve the transplanted cells viability. This system can act as a scaffold to allow cell adhesion/ maturation and protect them during the transplantation process. The cryogelation protocol was adjusted with different freezing regimes to produce a large macroporous structure. The in vitro results showed encouraging outcomes in which neurons were able to attach to the microcarriers and develop mature and three-dimensional neuronal morphologies. Although SH-SY5Y cells (a model dopamine neuron) were able to adhere, they were unable to proliferate and differentiate, meaning further work is needed for better cell growth. Finally, we suppose that these approaches could develop into potential supportive ways of tackling cell death issues posttransplantation and that they could lead to better knowledge and later, new cell therapy approaches for the treatment of PD.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Pharmacy
Subjects: Q Science > Q Science (General)
Date of First Compliant Deposit: 30 May 2024
Last Modified: 30 May 2024 10:46

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