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.

中文翻译：

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细胞替代疗法治疗退行性脊髓型颈椎病的前景

退行性脊髓型颈椎病 (DCM) 在中年期间隐匿出现，伴随神经功能恶化。它是发达国家非创伤性脊髓损伤的最常见原因，预计疾病患病率会随着人口老龄化而上升。虽然手术可以防止进一步恶化，但可能需要生物疗法来恢复晚期疾病的神经功能。细胞替代疗法一直过度关注创伤性脊髓损伤的治疗，但在 DCM 中却有着巨大的前景。我们通过回顾尸体和分子研究揭示的 DCM 的病理生理学来建立在本论文的基础上。少突胶质细胞和神经元的损失通过细胞凋亡发生。DCM 终末期疾病前的组织微环境与急性创伤后的组织微环境不同，并且在很多方面更利于接收外源细胞。我们强调了 DCM 中细胞替代的临床考虑因素，例如细胞类型的选择、时间和递送方法，以及生物治疗辅助。至关重要的是，疾病模型通常无法模仿人类病理学的特征。我们讨论了临床应用转化研究的方向。