Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
Exp Neurol. 2013 Oct;248:491-503. doi: 10.1016/j.expneurol.2013.07.010. Epub 2013 Jul 25.
Neural progenitor cells (NPCs) have shown modest potential and some side effects (e.g. allodynia) for treatment of spinal cord injury (SCI). In only a few cases, however, have NPCs shown promise at the chronic stage. Given the 1.275 million people living with chronic paralysis, there is a significant need to rigorously evaluate the cell types and methods for safe and efficacious treatment of this devastating condition. For the first time, we examined the pre-clinical potential of NPCs derived from human induced pluripotent stem cells (hiPSCs) to repair chronic SCI. hiPSCs were differentiated into region-specific (i.e. caudal) NPCs, then transplanted into a new, clinically relevant model of early chronic cervical SCI. We established the conditions for successful transplantation of caudalized hiPSC-NPCs and demonstrate their remarkable ability to integrate and produce multiple neural lineages in the early chronic injury environment. In contrast to prior reports in acute and sub-acute injury models, survival and integration of hiPSC-derived neural cells in the early chronic cervical model did not lead to significant improvement in forelimb function or induce allodynia. These data indicate that while hiPSCs show promise, future work needs to focus on the specific hiPSC-derivatives or co-therapies that will restore function in the early chronic injury setting.
神经祖细胞(NPC)在治疗脊髓损伤(SCI)方面显示出一定的潜力和一些副作用(例如感觉异常痛)。然而,在慢性阶段,NPC 仅在少数情况下显示出希望。考虑到有 127.5 万人患有慢性瘫痪,因此迫切需要严格评估细胞类型和方法,以安全有效地治疗这种毁灭性疾病。我们首次研究了源自人诱导多能干细胞(hiPSC)的 NPC 在修复慢性 SCI 方面的临床前潜力。将 hiPSC 分化为区域特异性(即尾侧)NPC,然后将其移植到新的、具有临床相关性的早期慢性颈 SCI 模型中。我们建立了成功移植尾侧化 hiPSC-NPC 的条件,并证明了它们在早期慢性损伤环境中整合和产生多种神经谱系的非凡能力。与急性和亚急性损伤模型中的先前报告相反,在早期慢性颈模型中,hiPSC 衍生的神经细胞的存活和整合并没有导致前肢功能的显著改善,也没有引起感觉异常痛。这些数据表明,虽然 hiPSC 显示出希望,但未来的工作需要集中在特定的 hiPSC 衍生物或联合疗法上,以恢复早期慢性损伤环境中的功能。