中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (1): 49-52.doi: 10.4103/1673-5374.169628

• 综述:退行性病与再生 • 上一篇    下一篇

神经干细胞替代治疗帕金森病的新策略

  

  • 收稿日期:2015-10-26 出版日期:2016-01-15 发布日期:2016-01-15

Tracking of iron-labeled human neural stem cells by magnetic resonance imaging in cell replacement therapy for Parkinson’s disease

Milagros Ramos-Gómez 1, 2, Alberto Martínez-Serrano 3   

  1. 1 Centre for Biomedical Technology, Polytechnic University of Madrid, Madrid, Spain
    2 Biomedical Research Networking Center of Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
    3 Department of Molecular Biology and Center of Molecular Biology “Severo Ochoa”, Autonomous University of Madrid-C.S.I.C, Madrid, Spain
  • Received:2015-10-26 Online:2016-01-15 Published:2016-01-15
  • Contact: Alberto Martínez-Serrano, Ph.D., amserrano@cbm.csic.es.
  • Supported by:

    Work at the author’s laboratories was supported by: To AMS: Instituto de Salud Carlos-III (RETICS TerCel RD12/0019/0013), Comunidad
    Autónoma de Madrid (S2010-BMD-2336), MINECO (SAF2010-17167) and the institutional grant of the Fundación Ramón Areces to the CBMSO. To MRG: Reina Sofia Foundation and Comunidad Autónoma Madrid (S2010-BMD-2460).

摘要:

干细胞研究的目标之一是在体外和体内产生可以代替某些急性病症和神经系统慢性疾病中丢失的神经元。如帕金森病,其特征为存在于黑质致密部位(黑质致密部)多巴胺能神经元的数量和功能渐进性丧失其完整性。无论是在临床前还是在临床试验背景中,干细胞以及更具体的神经干细胞,尤其是细胞替代疗法,构成了治疗帕金森病可行性的再生医学策略。尽管已有研究提供了干细胞替代策略在帕金森病治疗方面具有疗效的证据,但来源胎儿组织的胚胎肝细胞移植却因为实际情况和道德问题而无法在常规临床实践中得到实现。帕金森病细胞替代策略需要使用六到七个新鲜胎儿组织以提供足够的可移植细胞数量,并仅能用于单一患者,其中还存在移植细胞的死亡速率加快,缺乏再现性以及某些患者会产生严重不良副作用,如,运动障碍等问题。采用人类诱导多能干细胞和人类神经干细胞可以为规避上述问题提供潜在帮助,并成为多巴胺神经元的最佳替代来源。干细胞疗法有助于将细胞替代策略转化为临床治疗神经退行性疾病的可靠和有效的方法。

Abstract:

Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson’s disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation,self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time.

Key words: human neural stem cells, Parkinson’s disease, magnetic resonance imaging, magnetic nanoparticles, stem cell transplantation