Abstract
Degenerative cervical myelopathy (DCM) presents insidiously during middle-age with deterioration in neurological function. It accounts for the most common cause of non-traumatic spinal cord injury in developed countries and disease prevalence is expected to rise with the aging population. Whilst surgery can prevent further deterioration, biological therapies may be required to restore neurological function in advanced disease. Cell replacement therapy has been inordinately focused on treatment of traumatic spinal cord injury yet holds immense promise in DCM. We build upon this thesis by reviewing the pathophysiology of DCM as revealed by cadaveric and molecular studies. Loss of oligodendrocytes and neurons occurs via apoptosis. The tissue microenvironment in DCM prior to end-stage disease is distinct from that following acute trauma, and in many ways more favourable to receiving exogenous cells. We highlight clinical considerations for cell replacement in DCM such as selection of cell type, timing and method of delivery, as well as biological treatment adjuncts. Critically, disease models often fail to mimic features of human pathology. We discuss directions for translational research towards clinical application.
Funding source: Health and Medical Research Fund
Award Identifier / Grant number: 06172326
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: Health and Medical Research Fund (06172326) awarded to G.K. Shea.
Conflict of interest statement: K.M.C Cheung receives financial support from AOSpine, Avalon Spinecare, Medtronic, NuVasive, and Orthosmart. Otherwise, the authors have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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