中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (1): 10-16.doi: 10.4103/1673-5374.150638

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

诱导多能干细胞衍生的神经干细胞治疗脊髓损伤

  

  • 收稿日期:2014-12-24 出版日期:2015-01-15 发布日期:2015-01-15

Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury

Corinne A. Lee-Kubli 1, Paul Lu 1, 2, *   

  1. 1 Department of Neurosciences, University of California - San Diego, La Jolla, CA, USA
    2 Veterans Administration Medical Center, San Diego, CA, USA
  • Received:2014-12-24 Online:2015-01-15 Published:2015-01-15
  • Contact: Paul Lu, Ph.D., plu@ucsd.edu.
  • Supported by:

    This work was supported by grants from the Veterans Administration and the California Institute for Regenerative Medicine.

摘要:

脊髓损伤不仅破坏脊髓灰质神经元,而且伤害传输信号的白质轴突束,导致永久性的损伤平面以下的功能丧失。神经干细胞具有形成中间神经元的潜能,可桥接分离后的脊髓节段的功能连通,因此,对重建受损脊髓有很高的治疗潜力。一位健康的86岁男性的皮肤细胞诱导为多能干细胞并移植到C5半横断损伤免疫缺陷大鼠体内。脊髓损伤3个月后,移植的多能干细胞在脊髓损伤处存活,并分化为神经元和神经胶质,延伸出数万计轴突,事实上,分化的细胞几乎达到大鼠整个中枢神经系统的长度。这些分化的神经元沿着损伤脊髓白质生长,随即伸至灰质并与大鼠神经元形成突触。反过来,大鼠脊髓上运动神经元也伸至人多能干细胞移植物内并形成突触。这些结果表明,大鼠体内的神经元可轻松地突破体内的抑制因素长距离生长,多能干细胞有望成为脊髓损伤的治疗方法。尽管如此,在临床试验前,还需要进一步的试验更好地理解多能干细胞分化重编组原则,以便能取得最佳的潜在的治疗效果。

Abstract:

The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell therapies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.

Key words:  transplantation, axonal growth, axonal regeneration, neuroprotection, remyelination, differentiation, neuronal relay, human, astrocytes, neurons, oligodendrocytes, secondary degeneration