中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (13): 1190-1200.doi: 10.3969/j.issn.1673-5374.2013.13.004

• 原著:退行性病与再生 • 上一篇    下一篇

人牙乳头干细胞和人脑源性神经干细胞不适用治疗帕金森病？

  

  • 收稿日期:2012-12-21 修回日期:2013-04-03 出版日期:2013-05-05 发布日期:2013-05-05

Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson’s disease?

Hyung Ho Yoon1, Joongkee Min1, Nari Shin2, Yong Hwan Kim3, Jin-Mo Kim4, Yu-Shik Hwang5, Jun-Kyo Francis Suh4, Onyou Hwang2, Sang Ryong Jeon1   

  1. 1 Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    2 Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea
    3 Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA
    4 Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea
    5 Department of Maxillofacial Biomedical Engineering, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea
  • Received:2012-12-21 Revised:2013-04-03 Online:2013-05-05 Published:2013-05-05
  • Contact: Sang Ryong Jeon, M.D., Ph.D., Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Pungnap-2 dong, Songpa-gu, Seoul 138-736, Korea, srjeon@amc.seoul.kr.
  • About author:Hyung Ho Yoon★, M.S.

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摘要：

实验旨在认识人牙乳头干细胞和人脑源性神经干细胞是否可替换受损的多巴胺能神经元治疗帕金森病？实验给予大鼠右侧纹状注射6-羟基多巴胺，3周后分别于同侧纹状体注射磷酸盐缓冲溶液、早期人牙乳头干细胞和人脑源性神经干细胞。注射早期人牙乳头干细胞的大鼠于细胞移植后2周死于纹状体同源性恶性肿瘤。踏步试验显示，人脑源性神经干细胞移植不能改善帕金森病大鼠运动功能障碍。阿扑吗啡诱导旋转试验中，人脑源性神经干细胞不能改善帕金森病症状，但可使损伤纹状体的葡萄糖代谢明显降低。正电子发射断层扫描显示，多巴胺转运蛋白显像剂18F-N-3-氟丙基-2-β-甲酯基-3-β-(4-碘苯基)降托烷在人脑源性神经干细胞移植大鼠纹状体未明显增加。免疫组化染色显示，接受人脑源性神经干细胞移植大鼠的损伤纹状体，多巴胺能神经元标志物酪氨酸羟化酶和A9多巴胺能神经元标志物G 蛋白活化内向整流钾通道2表达阳性。说明早期人牙乳头干细胞进行移植后有成瘤性，而人脑源性神经干细胞移植后虽可分化为多巴胺能神经元，但这些神经元不能分泌多巴胺。这两种干细胞目前尚不适宜用于帕金森病的细胞替代疗法。

关键词: 神经再生, 干细胞, 细胞移植, 葡萄糖代谢, 人脑源性神经干细胞, 人牙乳头干细胞, 帕金森病, 正电子发射断层扫描, 基金资助文章

Abstract:

Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson’s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.