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 (25): 2360-2369.doi: 10.3969/j.issn.1673-5374.2013.25.007

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑肿瘤模型小鼠诱导的神经干细胞与脑肿瘤干细胞的相似性

  

  • 收稿日期:2013-06-01 修回日期:2013-08-25 出版日期:2013-09-05 发布日期:2013-09-05

Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

Guanqun Qiao1, Qingquan Li1, Gang Peng1, Jun Ma1, Hongwei Fan2, Yingbin Li1   

  1. 1 Department of Neurosurgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China

    2 Department of Pharmacology, the Third Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
  • Received:2013-06-01 Revised:2013-08-25 Online:2013-09-05 Published:2013-09-05
  • Contact: Yingbin Li, Ph.D., Professor, Department of Neurosurgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China, yingbinli65@sina.com.
  • About author:Guanqun Qiao, M.D. Guanqun Qiao and Qingquan Li contributed equally to this study.

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摘要：

目前研究认为脑胶质瘤起源于脑肿瘤干细胞，但脑肿瘤干细胞的来源尚不清楚。实验利用强力霉素诱导c-myc+/SV40Tag+/Tet-on+转基因小鼠建立脑肿瘤模型，观察从未经强力霉素诱导的转基因小鼠侧脑室室下区分离的正常神经干细胞，及从脑肿瘤模型小鼠脑室下区分离的诱导神经干细胞和从肿瘤组织分离的脑肿瘤干细胞的特性。结果发现，肿瘤干细胞染色体不稳定，其与诱导神经干细胞中与分化相关的溶酶体和自噬体明显少于正常神经干细胞，而增殖能力明显强于正常神经干细胞。同时3种细胞均可以向胶质纤维酸性蛋白阳性的胶质细胞和微管相关蛋白2阳性的神经元分化，但肿瘤干细胞和诱导神经干细胞分化的细胞nestin呈阳性。结果表明诱导神经干细胞与肿瘤干细胞相似，可能是脑肿瘤干细胞的起源。

关键词: 神经再生, 干细胞, 神经干细胞, 肿瘤干细胞, 脑室下区, 脑肿瘤, 转基因动物, 多向分化, 强力霉素

Abstract:

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

Key words: neural regeneration, stem cells, neural stem cells, brain tumor stem cells, subventricular zone, brain tumor, transgenic mouse model, multidirectional differentiation, doxycycline, neuroregeneration