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An investigation of canine mesenchymal stem cells and their secretome in the context of spinal cord injuryJohnson, Eustace; Wood, Chelsea R (University of Chester, 2020-05-26)Spinal cord injury (SCI) is a condition that has devastating effects on both humans and animals alike. Damage inflicted causes loss of neural tissue and secondary inflammatory mechanisms produce an inhibitory environment that results in partial or complete loss of motor and sensory functions. Additionally, SCI can cause multisystem issues such as organ failures, infections, muscle atrophy and decrease in mental health. Coupled with emotional and financial burdens, these effects can reduce quality of life. Mesenchymal Stem Cells (MSC) are known to have immunomodulatory, angiogenic and paracrine activity, all of which are beneficial to wound healing following SCI. Pre-clinical studies have shown encouraging results of MSC therapy for SCI, however replication of results has been difficult to achieve in the clinic. Dogs also suffer from SCI and show the same heterogenous nature and pathophysiology of SCI as humans. This provides a good potential clinical model for MSC therapies for SCI, as well as providing benefit in the veterinary clinic. Therefore, the overall aim of this study was to assess if canine MSC (cMSC) and cMSC secretome (conditioned medium; CM) could potentially be used for treatment of SCI in veterinary clinics, simultaneously providing model data that could be translated into the human clinic. It was first required to confirm efficacy of cMSC when used to treat other conditions in dogs, such as arthritis, along with safety of autologous transplantation. Characterisation of both cMSC phenotype and paracrine (angiogenic and neurogenic) activity was confirmed using ISCT criteria and the established cell lines EA.hy926 and SH-SY5Y. Further examination showed that exposure to certain elements of the injured spinal cord, such as CSPG which are found within the inhibitory glial scar, exerted some effects on cMSC and cMSC angiogenic and neurogenic paracrine activity. To finish, the study aimed to assess the effect of cMSC CM on an ex vivo model of the spinal cord, a multicellular environment and it was found that cMSC CM increased astrocyte reactivity but reduced neuronal maturation and growth, suggesting that cMSC paracrine activity depends in part on the spinal cord microenvironment. Overall, this study has shown that cMSC, in particular cMSC CM, could be used as complete or partial treatment for SCI in dogs.