Spinal cord injury (SCI) affects millions of people worldwide. Neural progenitor cell (NPC) transplantation is a promising treatment for regenerating lost spinal cord tissue and restoring neurological function after SCI. We conducted a literature search and found that less than a quarter of experimental rodent cell and tissue transplantation studies have investigated anatomical outcomes at longer than 4 months post-transplantation. This is a critical topic to investigate, given that stem and progenitor cell therapies would need to remain in place throughout the lifetime of an individual. We sought to determine how commonly assessed anatomical outcomes evolve between early and far chronic time-points post-NPC transplantation. At either 8 weeks or 26 weeks following transplantation of NPCs into sites of cervical SCI, we evaluated graft neuronal density, astroglial cell density, graft axon outgrowth, and regeneration of host axon populations into grafts in male and female mice. We found that graft neuronal density does not change over time, but the numbers of graft-associated astrocytes and glial fibrillary acidic protein intensity is significantly increased in the far chronic phase compared with the early chronic time-point. In addition, graft axon outgrowth was significantly decreased at 26 weeks post-transplantation compared with 8 weeks post-transplantation. In contrast, corticospinal axon regeneration into grafts was not diminished over time, but rather increased significantly from early to far chronic periods. Interestingly, we found that graft neuronal density is significantly influenced by sex of the host animal, suggesting that sex-dependent processes may shape graft composition over time. Collectively, these results demonstrate that NPC transplants are dynamic and that commonly assessed outcome measures associated with graft efficacy evolve over the weeks to months post-transplantation into the spinal cord.

中文翻译：

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小鼠脊髓神经祖细胞移植后早期慢性和远慢性时间点之间解剖结果的差异。

脊髓损伤 (SCI) 影响着全世界数百万人。神经祖细胞 (NPC) 移植是 SCI 后再生丢失的脊髓组织和恢复神经功能的一种有前景的治疗方法。我们进行了文献检索，发现只有不到四分之一的实验性啮齿动物细胞和组织移植研究调查了移植后 4 个月以上的解剖结果。鉴于干细胞和祖细胞疗法需要在个体的一生中保持不变，这是一个需要研究的关键主题。我们试图确定鼻咽癌移植后早期和长期时间点之间通常评估的解剖结果如何演变。在将 NPC 移植到颈椎 SCI 部位后 8 周或 26 周，我们评估了雄性和雌性小鼠的移植神经元密度、星形胶质细胞密度、移植轴突生长以及宿主轴突群在移植物中的再生。我们发现移植物神经元密度不随时间变化，但与早期慢性时间点相比，远慢性期移植物相关星形胶质细胞的数量和胶质纤维酸性蛋白强度显着增加。此外，与移植后8周相比，移植后26周的移植物轴突生长显着减少。相比之下，皮质脊髓轴突再生成移植物并没有随着时间的推移而减少，而是从早期到长期慢性期显着增加。有趣的是，我们发现移植神经元密度明显受到宿主动物性别的影响，这表明性别依赖性过程可能会随着时间的推移影响移植物的组成。总的来说，这些结果表明鼻咽癌移植是动态的，并且与移植物功效相关的常用评估结果测量在移植到脊髓后数周至数月内不断变化。