Inoue Mitsuhiro, Yamaguchi Ryo, He Ching Chi Jimmy, Ikeda Atsushi, Okano Hideyuki, Kohyama Jun
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Regenerative & Cellular Medicine Kobe Center, Sumitomo Pharma Co., Ltd., Kobe, Hyogo, Japan.
Stem Cell Investig. 2023 Mar 10;10:6. doi: 10.21037/sci-2022-037. eCollection 2023.
Spinal cord injury (SCI) is damage to the spinal cord due to trauma or health conditions, resulting in lesions in the spinal cord. Currently, available treatment includes surgical intervention to decompress or stabilize a dislocated loose spine, steroid drugs to reduce inflammation, and subsequent rehabilitation. As there is a rising number of SCI globally, radical treatments to recover spinal cord functions have become highly anticipated. The development of new treatments is indeed progressing. Various therapeutic drug candidates are being developed in clinical trials, including neuroprotective/neurotrophic factors, antibodies for repulsive guidance molecules, and cell transplantation. Among them, with advances in stem cell biology, cell transplantation therapy is currently a promising therapeutic development for SCI. In particular, there have been various reports regarding the realization of regenerative medicine using human induced pluripotent stem cells (iPSCs). This review will introduce the advantages of cell-based therapy based on iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs) and some of their mechanisms of action for functional improvement, which have recently been elucidated. Potential challenges and methodologies to realize the clinical application of iPSC-NS/PCs not only for the subacute phase but also for the chronic phase of SCI will be presented. Finally, we also introduce recent research with a view to the clinical application of spinal cord regenerative therapy and discuss future prospects.
脊髓损伤(SCI)是指由于外伤或健康状况导致脊髓受损,进而引起脊髓病变。目前,可用的治疗方法包括手术干预以解除脱位或稳定松动的脊柱、使用类固醇药物减轻炎症以及后续的康复治疗。由于全球范围内脊髓损伤的病例数量不断增加,恢复脊髓功能的根治性治疗方法备受期待。新治疗方法的研发确实在不断推进。各种治疗候选药物正在临床试验中进行研发,包括神经保护/神经营养因子、针对排斥导向分子的抗体以及细胞移植。其中,随着干细胞生物学的发展,细胞移植疗法目前是脊髓损伤治疗领域一个有前景的发展方向。特别是,关于使用人类诱导多能干细胞(iPSC)实现再生医学的报道层出不穷。本综述将介绍基于iPSC衍生的神经干细胞/祖细胞(iPSC-NS/PCs)的细胞治疗的优势及其一些改善功能的作用机制,这些机制最近已得到阐明。还将介绍实现iPSC-NS/PCs不仅在脊髓损伤亚急性期而且在慢性期临床应用的潜在挑战和方法。最后,我们还将介绍近期关于脊髓再生治疗临床应用的研究,并探讨未来前景。