Zheng Xiaolong, Wang Wei
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Key Laboratory of Neurological Diseases of Chinese Ministry of Education, the School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
J Biomed Res. 2022 Jun 28;36(5):312-320. doi: 10.7555/JBR.36.20220012.
Spinal cord injury (SCI) leads to permanent deficits in neural function without effective therapies, which places a substantial burden on families and society. Astrocytes, the major glia supporting the normal function of neurons in the spinal cord, become active and form glial scars after SCI, which has long been regarded as a barrier for axon regeneration. However, recent progress has indicated the beneficial role of astrocytes in spinal repair. During the past three decades, astrocyte transplantation for SCI treatment has gained increasing attention. In this review, we first summarize the progress of using rodent astrocytes as the primary step for spinal repair. Rodent astrocytes can survive well, migrate extensively, and mature in spinal injury; they can also inhibit host reactive glial scar formation, stimulate host axon regeneration, and promote motor, sensory, respiratory, and autonomic functional recovery. Then, we review the progress in spinal repair by using human astrocytes of various origins, including the fetal brain, fetal spinal cord, and pluripotent stem cells. Finally, we introduce some key questions that merit further research in the future, including rapid generation of large amounts of human astrocytes with high purity, identification of the right origins of astrocytes to maximize neural function improvement while minimizing side effects, testing human astrocyte transplantation in chronic SCI, and verification of the long-term efficacy and safety in large animal models.
脊髓损伤(SCI)导致神经功能永久性缺陷,且尚无有效治疗方法,这给家庭和社会带来了沉重负担。星形胶质细胞是支持脊髓中神经元正常功能的主要神经胶质细胞,在脊髓损伤后会变得活跃并形成胶质瘢痕,长期以来一直被视为轴突再生的障碍。然而,最近的进展表明星形胶质细胞在脊髓修复中具有有益作用。在过去三十年中,星形胶质细胞移植用于SCI治疗越来越受到关注。在这篇综述中,我们首先总结了使用啮齿动物星形胶质细胞作为脊髓修复第一步的进展。啮齿动物星形胶质细胞能够很好地存活、广泛迁移并在脊髓损伤处成熟;它们还能抑制宿主反应性胶质瘢痕形成,刺激宿主轴突再生,并促进运动、感觉、呼吸和自主神经功能恢复。然后,我们回顾了使用各种来源的人类星形胶质细胞进行脊髓修复的进展,包括胎儿脑、胎儿脊髓和多能干细胞。最后,我们介绍了一些未来值得进一步研究的关键问题,包括快速大量生成高纯度的人类星形胶质细胞、确定星形胶质细胞的合适来源以在最小化副作用的同时最大化神经功能改善、在慢性SCI中测试人类星形胶质细胞移植以及在大型动物模型中验证长期疗效和安全性。