Division of Neurodegenerative Diseases, Department of Neurology, and Department of Neurosurgery, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Department of Neurology, Hannover Medical School, Hannover, Germany; Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Division of Biology, California Institute of Technology, Pasadena, California, USA; Center for Regenerative Therapies Dresden, Dresden, Germany.
Stem Cells Transl Med. 2014 Apr;3(4):458-69. doi: 10.5966/sctm.2013-0117. Epub 2014 Feb 20.
Adult neural progenitor cells (aNPC) are a potential autologous cell source for cell replacement in neurologic diseases or for cell-based gene therapy of neurometabolic diseases. Easy accessibility, long-term expandability, and detailed characterization of neural progenitor cell (NPC) properties are important requisites for their future translational/clinical applications. aNPC can be isolated from different regions of the adult human brain, including the accessible subcortical white matter (aNPCWM), but systematic studies comparing long-term expanded aNPCWM with aNPC from neurogenic brain regions are not available. Freshly isolated cells from subcortical white matter and hippocampus expressed oligodendrocyte progenitor cell markers such as A2B5, neuron-glial antigen 2 (NG2), and oligodendrocyte transcription factor 2 (OLIG2) in ∼20% of cells but no neural stem cell (NSC) markers such as CD133 (Prominin1), Nestin, SOX2, or PAX6. The epidermal growth factor receptor protein was expressed in 18% of aNPCWM and 7% of hippocampal aNPC (aNPCHIP), but only a small fraction of cells, 1 of 694 cells from white matter and 1 of 1,331 hippocampal cells, was able to generate neurospheres. Studies comparing subcortical aNPCWM with their hippocampal counterparts showed that both NPC types expressed mainly markers of glial origin such as NG2, A2B5, and OLIG2, and the NSC/NPC marker Nestin, but no pericyte markers. Both NPC types were able to produce neurons, astrocytes, and oligodendrocytes in amounts comparable to fetal NSC. Whole transcriptome analyses confirmed the strong similarity of aNPCWM to aNPCHIP. Our data show that aNPCWM are multipotent NPC with long-term expandability similar to NPC from hippocampus, making them a more easily accessible source for possible autologous NPC-based treatment strategies.
成人神经祖细胞 (aNPC) 是神经退行性疾病细胞替代治疗或神经代谢性疾病基于细胞的基因治疗的潜在自体细胞来源。神经祖细胞 (NPC) 易于获取、长期可扩增性和 NPC 特性的详细特征是其未来转化/临床应用的重要要求。aNPC 可从成人大脑的不同区域分离出来，包括可接近的皮质下白质 (aNPCWM)，但尚未有比较长期扩增的 aNPCWM 与神经发生区域的 aNPC 的系统研究。来自皮质下白质和海马体的新鲜分离细胞在约 20%的细胞中表达少突胶质祖细胞标志物，如 A2B5、神经元-神经胶质抗原 2 (NG2) 和少突胶质转录因子 2 (OLIG2)，但没有神经干细胞 (NSC) 标志物，如 CD133 (Prominin1)、巢蛋白、SOX2 或 PAX6。表皮生长因子受体蛋白在 aNPCWM 和 aNPC 的海马体中分别表达 18%和 7%，但只有一小部分细胞能够生成神经球，来自白质的 694 个细胞中有 1 个，来自海马体的 1331 个细胞中有 1 个。比较皮质下 aNPCWM 与海马体对应物的研究表明，两种 NPC 类型均主要表达神经胶质来源的标志物，如 NG2、A2B5 和 OLIG2，以及 NSC/NPC 标志物巢蛋白，但没有周细胞标志物。两种 NPC 类型均能够产生神经元、星形胶质细胞和少突胶质细胞，其数量与胎鼠 NSC 相当。全转录组分析证实了 aNPCWM 与 aNPC 的海马体高度相似。我们的数据表明，aNPCWM 是具有长期可扩增性的多能 NPC，与海马体来源的 NPC 相似，使其成为更易于获取的潜在自体 NPC 治疗策略的细胞来源。
