Neural stem cells (NSCs) differentiate into both neurons and glia, and strategies using human NSCs have the potential to restore function following spinal cord injury (SCI). However, the time period of maturation for human NSCs in adult injured CNS is not well defined, posing fundamental questions about the design and implementation of NSC-based therapies. This work assessed human H9 NSCs that were implanted into sites of SCI in immunodeficient rats over a period of 1.5 years. Notably, grafts showed evidence of continued maturation over the entire assessment period. Markers of neuronal maturity were first expressed 3 months after grafting. However, neurogenesis, neuronal pruning, and neuronal enlargement continued over the next year, while total graft size remained stable over time. Axons emerged early from grafts in very high numbers, and half of these projections persisted by 1.5 years. Mature astrocyte markers first appeared after 6 months, while more mature oligodendrocyte markers were not present until 1 year after grafting. Astrocytes slowly migrated from grafts. Notably, functional recovery began more than 1 year after grafting. Thus, human NSCs retain an intrinsic human rate of maturation, despite implantation into the injured rodent spinal cord, yet they support delayed functional recovery, a finding of great importance in planning human clinical trials.

中文翻译：

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长时间的人类神经干细胞成熟支持受损啮齿动物中枢神经系统的恢复

神经干细胞（NSC）分化为神经元和神经胶质，使用人类NSC的策略具有在脊髓损伤（SCI）后恢复功能的潜力。然而，成人神经损伤后成人中枢神经干细胞成熟的时间还没有很好的定义，这对基于神经干细胞治疗的设计和实施提出了根本性的问题。这项工作评估了人类H9神经干细胞在1.5年内植入免疫缺陷大鼠SCI的部位。值得注意的是，移植物显示出在整个评估期内持续成熟的证据。神经元成熟的标志物首先在移植后3个月表达。然而，在接下来的一年中，神经发生，神经元修剪和神经元扩大继续发生，而总移植物尺寸随时间保持稳定。轴突从移植物中大量出现，这些预测的一半持续了1.5年。成熟的星形胶质细胞标志物在6个月后首次出现，而更成熟的少突胶质细胞标志物直到移植后1年才出现。星形胶质细胞从移植物中缓慢迁移。值得注意的是，移植后1年以上开始功能恢复。因此，尽管将人类NSC植入受伤的啮齿动物脊髓中，它仍然具有人类固有的成熟率，但它们支持功能恢复延迟，这一发现在计划人类临床试验中具有重要意义。