中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1356-1358.doi: 10.4103/1673-5374.165209

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

中枢神经系统的细胞替代策略?

  

  • 收稿日期:2015-06-19 出版日期:2015-09-28 发布日期:2015-09-28

Cell replacement therapy for central nervous system diseases

Danju Tso, Randall D. McKinnon   

  1. Department of Surgery (Neurosurgery), Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
  • Received:2015-06-19 Online:2015-09-28 Published:2015-09-28
  • Contact: Randall D. McKinnon, Ph.D., mckinnon@rwjms.rutgers.edu.
  • Supported by:

    This study was supported by grants from the New Jersey Commission on Spinal Cord Research (11-0015-SCR).

摘要:

大脑和脊髓不能自主替换那些因为创伤性损伤或疾病而丢失的神经元或者支持神经胶质细胞。临床前研究发现,神经干细胞和祖细胞移植可以促进脑功能恢复。为了使细胞移植具有临床可行性,需要有组织相容性、无伦理争议和无致瘤性的种子细胞来源。策略之一是生成患者需要置换的特异性细胞,将自体成纤维细胞重新编程进入多能干细胞,然后其可以分化成所需的移植细胞。然而,多能干细胞移植效用是有限的,因为它们会保留原始细胞与肿瘤内在生成潜力。最近一项新技术直接将重编程的成纤维细胞延伸到最终移植细胞内,其中没有诱导性多能干细胞的介入,从而避免了多能性的风险。由于这两种类型的重编程转换效率非常低,因此需要扩增培养中的细胞,但这样会导致染色体的不稳定和肿瘤形成。因此为了提高重编程细胞临床应用的可行性,必须提高重编程的成功效率。

Abstract:

The brain and spinal cord can not replace neurons or supporting glia that are lost through traumatic injury or disease. In pre-clinical studies, however, neural stem and progenitor cell transplants can promote functional recovery. Thus the central nervous system is repair competent but lacks endogenous stem cell resources. To make transplants clinically feasible, this field needs a source of histocompatible, ethically acceptable and non-tumorgenic cells. One strategy to generate patient-specific replacement cells is to reprogram autologous cells such as fibroblasts into pluripotent stem cells which can then be differentiated into the required cell grafts. However, the utility of pluripotent cell derived grafts is limited since they can retain founder cells with intrinsic neoplastic potential. A recent extension of this technology directly reprograms fibroblasts into the final graftable cells without an induced pluripotent stem cell intermediate, avoiding the pluripotent caveat. For both types of reprogramming the conversion efficiency is very low resulting in the need to amplify the cells in culture which can lead to chromosomal instability and neoplasia. Thus to make reprogramming biology clinically feasible, we must improve the efficiency. The ultimate source of replacement cells may reside in directly reprogramming accessible cells within the brain.

Key words: in vivo direct reprogramming, spinal cord injury, trauma, personalized medicine, induced pluripotent stem cell, embryonic stem cells