iPSC 衍生的神经前体细胞:脊髓损伤细胞移植治疗的潜力。

iPSC-derived neural precursor cells: potential for cell transplantation therapy in spinal cord injury.

机构信息

Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.

Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjukuku, Tokyo, 160-8582, Japan.

出版信息

Cell Mol Life Sci. 2018 Mar;75(6):989-1000. doi: 10.1007/s00018-017-2676-9. Epub 2017 Oct 9.

Abstract

A number of studies have demonstrated that transplantation of neural precursor cells (NPCs) promotes functional recovery after spinal cord injury (SCI). However, the NPCs had been mostly harvested from embryonic stem cells or fetal tissue, raising the ethical concern. Yamanaka and his colleagues established induced pluripotent stem cells (iPSCs) which could be generated from somatic cells, and this innovative development has made rapid progression in the field of SCI regeneration. We and other groups succeeded in producing NPCs from iPSCs, and demonstrated beneficial effects after transplantation for animal models of SCI. In particular, efficacy of human iPSC-NPCs in non-human primate SCI models fostered momentum of clinical application for SCI patients. At the same time, however, artificial induction methods in iPSC technology created alternative issues including genetic and epigenetic abnormalities, and tumorigenicity after transplantation. To overcome these problems, it is critically important to select origins of somatic cells, use integration-free system during transfection of reprogramming factors, and thoroughly investigate the characteristics of iPSC-NPCs with respect to quality management. Moreover, since most of the previous studies have focused on subacute phase of SCI, establishment of effective NPC transplantation should be evaluated for chronic phase hereafter. Our group is currently preparing clinical-grade human iPSC-NPCs, and will move forward toward clinical study for subacute SCI patients soon in the near future.

摘要

许多研究表明,神经前体细胞(NPCs)的移植可以促进脊髓损伤(SCI)后的功能恢复。然而,这些 NPC 大多是从胚胎干细胞或胎儿组织中提取的,这引发了伦理方面的担忧。山中伸弥及其同事建立了诱导多能干细胞(iPSCs),可以从体细胞中产生,这一创新性的发展在 SCI 再生领域取得了快速进展。我们和其他小组成功地从 iPSCs 中产生了 NPCs,并在 SCI 动物模型中移植后证明了其有益效果。特别是,人类 iPSC-NPCs 在非人类灵长类动物 SCI 模型中的疗效为 SCI 患者的临床应用提供了动力。然而,与此同时,iPSC 技术中的人工诱导方法产生了包括遗传和表观遗传异常以及移植后致瘤性等其他问题。为了克服这些问题,选择体细胞的起源、在重编程因子转染过程中使用无整合系统以及彻底研究 iPSC-NPCs 的特性以进行质量管理至关重要。此外,由于之前的大多数研究都集中在 SCI 的亚急性期,因此此后应评估在慢性期建立有效的 NPC 移植的效果。我们小组目前正在制备临床级别的人类 iPSC-NPCs,并将在不久的将来为亚急性 SCI 患者的临床研究做好准备。

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