Olushanu, Modinat Liadi; (2021) Repair of Spinal Cord Injuries by Transplanting Olfactory Mucosal Ensheathing Cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis investigates spinal cord injuries' repair by transplantation of cultured olfactory ensheathing cells derived from the olfactory mucosa. This thesis's primary research aims to identify how olfactory ensheathing cells from olfactory mucosa can effectively treat spinal cord injuries. The questions raised in this study address the challenges when attempting to translate the lab research to clinical application. In our previous protocol, the number of olfactory ensheathing cells obtained from the olfactory mucosa is limited. Methods to increase the olfactory ensheathing cells population from the olfactory mucosa have been explored in this thesis. Conditions to expand the volume of the cell transplant were optimised by encapsulating the cells in collagen. In vitro assays of organotypic slice cultures and dorsal root ganglions were used to determine the ability of olfactory mucosa ensheathing cells encapsulated in collagen in recruiting axons. Spinal cord injury animal model with bilateral dorsal column lesion was used to test effects on promoting regeneration of damaged axons and restore the loss of motor and sensory functions by transplanting the cell-collagen scaffold into the lesioned area. The increase of the olfactory ensheathing cells population from olfactory mucosa culture was achieved using forskolin and N2 supplement. Cells were successfully encapsulated into a biomaterial (collagen type 1) for ease of use and cell transplant volume expansion. This study demonstrates that the olfactory ensheathing cells population in olfactory mucosa can be increased significantly. The increase contributes to restoring functions after a bilateral column lesion in rat spinal cord injuries models. The results of this study demonstrate: 1. Improvement of olfactory ensheathing cell cultures obtained from the olfactory mucosa can be achieved. 2. Improved olfactory mucosa - olfactory ensheathing cell cultures increases the therapeutic potential of using olfactory ensheathing cells to cure spinal cord injuries since olfactory ensheathing cells can be obtained from tissue biopsied from a region that is quickly and safely accessed. 3. Combination of improved olfactory mucosa - olfactory ensheathing cell cultures and collagen expands the transplant volume by more efficient use of the number of cells available for easy handling and bridging large cavity in spinal cord injuries.

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