Kitagawa Takahiro, Nagoshi Narihito, Okano Hideyuki, Nakamura Masaya
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Neurospine. 2022 Dec;19(4):935-945. doi: 10.14245/ns.2244628.314. Epub 2022 Dec 31.
A spinal cord injury (SCI) is a destructive event that causes a permanent deficit in neurological function because of poor regenerative potential. Transplantation therapies have attracted attention for restoration of the injured spinal cord, and transplantation of neural precursor cells (NPCs) has been studied worldwide. Several groups have demonstrated functional recovery via this therapeutic intervention due to the multiple beneficial effects of NPC transplantation, such as reconstruction of neuronal circuits, remyelination of axons, and neuroprotection by trophic factors. Our group developed a method to induce NPCs from human induced pluripotent stem cells (hiPSCs) and established a transplantation strategy for SCI. Functional improvement in SCI animals treated with hiPSC-NPCs was observed, and the safety of transplanting these cells was evaluated from multiple perspectives. With selection of a safe cell line and pretreatment of the cells to encourage maturation and differentiation, hiPSC-NPC transplantation therapy is now in the clinical phase of testing for subacute SCI. In addition, a research challenge will be to expand the efficacy of transplantation therapy for chronic SCI. More comprehensive strategies involving combination treatments are required to treat this problematic situation.
脊髓损伤（SCI）是一种破坏性事件，由于再生潜力不佳，会导致神经功能永久性缺损。移植疗法已引起人们对损伤脊髓修复的关注，神经前体细胞（NPCs）移植已在全球范围内得到研究。由于NPC移植具有多种有益作用，如重建神经回路、轴突髓鞘再生以及营养因子的神经保护作用，几个研究团队已通过这种治疗干预证明了功能恢复。我们团队开发了一种从人诱导多能干细胞（hiPSCs）诱导生成NPCs的方法，并建立了一种针对SCI的移植策略。观察到用hiPSC-NPCs治疗的SCI动物功能有所改善，并从多个角度评估了移植这些细胞的安全性。通过选择安全的细胞系并对细胞进行预处理以促进成熟和分化，hiPSC-NPC移植疗法目前正处于亚急性SCI测试的临床阶段。此外，一项研究挑战将是扩大慢性SCI移植疗法的疗效。需要更全面的涉及联合治疗的策略来应对这种棘手的情况。
