Tickle, Jacqueline Amanda (2017) Engineering neural cells in implantable materials. Doctoral thesis, Keele University.

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Abstract

A key goal in regenerative therapy is to improve outcomes following the devastating consequences of spinal cord injury. Yearly, between 250,000 to 500,000 people suffer
permanent injury to the spinal cord. The cost to the individual, their families and society is substantial. Modest success in clinical trials has offered hope. However, there remain a number of challenges still to be met in respect of a combinatorial approach that offers safe delivery of grafts, to promote recovery and regeneration in the injured spinal cord.

In this context astrocytes have shown promise as a cell transplant population. This project aimed to develop strategies to engineer astrocytes to improve their repair capacity as a cell transplant population for regenerative applications. Specifically, methods were attempted using applied magnetic fields to i) enhance magnetic nanoparticle mediated gene delivery in primary-derived cortical astrocytes, and ii) achieve high levels of magnetic particle loading and long term retention in cells by tailoring particle magnetite content, improving
utility for non-invasive imaging applications. Further, high cell loss during surgical delivery of transplant cells has prompted the need to develop protective cell delivery systems for neural cells. Use of a 3-dimensional collagen hydrogel was investigated for this purpose, and the capacity to image particle labelled intra-gel astrocytes evaluated.

The findings show that a tailored combination of magnetic field parameters increased transfection efficiency, and enhanced transgene expression in astrocytes. Second,
astrocytes showed rapid, highly efficient but safe accumulation and long term retention of high magnetite content particles. Third, collagen hydrogels offered a protective environment conducive to cell transplant delivery. Finally, within the hydrogel, magnetic particle labelled astrocytes retained their utility for cell tracking by MRI over an extended time frame.

Item Type: Thesis (Doctoral)
Subjects: Q Science > QP Physiology
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Lisa Bailey
Date Deposited: 20 Jul 2017 09:24
Last Modified: 20 Jul 2017 09:24
URI: http://eprints.keele.ac.uk/id/eprint/3774

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