创伤性脊髓损伤（SCI）导致神经元、少突胶质细胞和星形胶质细胞的丧失。目前SCI的干预措施包括减压手术、抗炎疗法和康复计划。然而，这些方法并不能提供再生的解决方案来替代丧失的细胞、纤维束和回路。神经干细胞/祖细胞（NPC）移植是一种有希望的策略，旨在促进再生。然而，NPC的分化仍然不一致，从而导致功能恢复不理想。因此，我们之前已经改造了有寡突发生倾向的NPC（oNPCs），并在胸椎SCI模型中证明了其疗效。由于大多数SCI患者患的是颈部损伤，本研究的目标是产生人诱导多能干细胞衍生的有寡突发生倾向的NPC（hiPSC-oNPCs），并利用临床相关的鼠颈损伤模型对这些细胞进行体外和体内特性评估。移植后，oNPCs在损伤的向头和向尾部分迁移，显示出向少突胶质细胞优先分化的特点。组织病理学评估显示，oNPC移植促进了组织保护同时减少了星形胶质增生。此外，oNPC移植促进了有存留组织的重髓鞘化。功能分析表明，oNPC移植大鼠的前肢握力、步态和运动功能均有改善。重要的是，oNPC移植没有加重神经病理性疼痛或诱导肿瘤形成。总之，这些发现强调了oNPC在促进颈部SCI功能恢复和组织病理学改善方面的治疗潜力。这一证据有待进一步研究以优化和推进这种有前景的基于细胞的治疗方法。© 作者们 2023. 由牛津大学出版社发布。

Traumatic spinal cord injury (SCI) results in the loss of neurons, oligodendrocytes, and astrocytes. Present interventions for SCI include decompressive surgery, anti-inflammatory therapies, and rehabilitation programs. Nonetheless, these approaches do not offer regenerative solutions to replace the lost cells, fiber tracts, and circuits. Neural stem/progenitor cell (NPC) transplantation is a promising strategy that aims to encourage regeneration. However, NPC differentiation remains inconsistent, thus, contributing to suboptimal functional recovery. As such, we have previously engineered oligodendrogenically biased NPCs (oNPCs) and demonstrated their efficacy in a thoracic model of SCI. Since the majority of patients with SCI experience cervical injuries, our objective in the current study was to generate human induced pluripotent stem cell-derived oNPCs (hiPSC-oNPCs) and to characterize these cells in vitro and in vivo, utilizing a clinically relevant rodent model of cervical SCI. Following transplantation, the oNPCs engrafted, migrated to the rostral and caudal regions of the lesion, and demonstrated preferential differentiation toward oligodendrocytes. Histopathological evaluations revealed that oNPC transplantation facilitated tissue preservation while diminishing astrogliosis. Moreover, oNPC transplantation fostered remyelination of the spared tissue. Functional analyses indicated improved forelimb grip strength, gait, and locomotor function in the oNPC-transplanted rats. Importantly, oNPC transplantation did not exacerbate neuropathic pain or induce tumor formation. In conclusion, these findings underscore the therapeutic potential of oNPCs in promoting functional recovery and histopathological improvements in cervical SCI. This evidence warrants further investigation to optimize and advance this promising cell-based therapeutic approach.© The Author(s) 2023. Published by Oxford University Press.