Balgrist University Hospital, Zurich, Switzerland.
University Hospital Zurich, Zurich, Switzerland.
Neurorehabil Neural Repair. 2020 Aug;34(8):758-768. doi: 10.1177/1545968320935815. Epub 2020 Jul 23.
. Given individuals with spinal cord injury (SCI) approaching 2 million, viable options for regenerative repair are desperately needed. Human central nervous system stem cells (HuCNS-SC) are self-renewing, multipotent adult stem cells that engraft, migrate, and differentiate in appropriate regions in multiple animal models of injured brain and spinal cord. Preclinical improved SCI locomotor function provided rationale for the first-in-human SCI clinical trial of HuCNS-SC cells. Evidence of feasibility and long-term safety of cell transplantation into damaged human cord is needed to foster translational progression of cellular therapies. . A first-ever, multisite phase I/IIa trial involving surgical transplantation of 20 million HuCNS-SC cells into the thoracic cord in 12 AIS A or B subjects (traumatic, T2-T11 motor-complete, sensory-incomplete), aged 19 to 53 years, demonstrated safety and preliminary efficacy. Six-year follow-up data were collected (sensory thresholds and neuroimaging augmenting clinical assessments). . The study revealed short- and long-term surgical and medical safety (well-tolerated immunosuppression in population susceptible to infections). Preliminary efficacy measures identified 5/12 with reliable sensory improvements. Unfortunately, without thoracic muscles available for manual muscle examination, thoracic motor changes could not be measured. Lower limb motor scores did not change during the study. Cervical cord imaging revealed, no tumor formation or malformation of the lesion area, and secondary supralesional structural changes similar to SCI control subjects. . Short- and long-term safety and feasibility support the consideration of cell transplantation for patients with complete and incomplete SCI. This report is an important step to prepare, foster, and maintain the therapeutic development of cell transplantation for human SCI.
. 鉴于患有脊髓损伤 (SCI) 的个体接近 200 万，因此迫切需要可行的再生修复选择。人中枢神经系统干细胞 (HuCNS-SC) 是自我更新的多能成体干细胞，在多种损伤脑和脊髓的动物模型中，可在适当的区域植入、迁移和分化。临床前研究改善了 SCI 运动功能，为首次 HuCNS-SC 细胞治疗人类 SCI 的临床试验提供了依据。需要证明细胞移植入受损人类脊髓的可行性和长期安全性，以促进细胞治疗的转化进展。. 这是首次涉及在 12 名 AIS A 或 B 受试者（外伤性，T2-T11 运动完全性，感觉不完全性）的胸髓中移植 2000 万 HuCNS-SC 细胞的多中心、1/2a 期临床试验，年龄在 19 至 53 岁之间，该试验证明了安全性和初步疗效。收集了六年的随访数据（感觉阈值和神经影像学增强临床评估）。. 该研究揭示了短期和长期的手术和医疗安全性（在易感染人群中耐受良好的免疫抑制）。初步疗效措施确定了 12 名中有 5 名具有可靠的感觉改善。不幸的是，由于没有胸肌用于手动肌肉检查，因此无法测量胸肌变化。在研究过程中，下肢运动评分没有变化。颈椎脊髓成像显示，没有肿瘤形成或病变区域畸形，继发性超病变结构变化与 SCI 对照组相似。. 短期和长期安全性和可行性支持考虑对完全性和不完全性 SCI 患者进行细胞移植。本报告是为细胞移植治疗人类 SCI 做准备、促进和维持治疗性开发的重要一步。
