Oliver-De La Cruz Jorge, Carrión-Navarro Josefa, García-Romero Noemí, Gutiérrez-Martín Antonio, Lázaro-Ibáñez Elisa, Escobedo-Lucea Carmen, Perona Rosario, Belda-Iniesta Cristobal, Ayuso-Sacido Angel
Centro Integral Oncológico Clara Campal (CIOCC) and Instituto de Medicina Molecular Aplicada (IMMA), Hospital de Madrid Foundation, Madrid, Spain.
Nanomedicine Laboratory, Instituto Madrileño de Estudios Avanzados IMDEA nanoscience, Madrid, Spain.
PLoS One. 2014 Jun 5;9(6):e99253. doi: 10.1371/journal.pone.0099253. eCollection 2014.
A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established.
We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo.
We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+).
Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures.
许多神经退行性疾病随着髓磷脂的丧失而进展,这使得它们成为基于内源性神经/胶质祖细胞的动员或分离、体外扩增以及进一步植入的细胞替代疗法开发的候选疾病。在正常成人大脑皮质下白质的胶质祖细胞池中已分离出表达A2B5或PDGFRA/CNP的细胞,所有这些细胞均表现出胶质祖细胞特征。然而,这一细胞池的异质性和分化潜能尚未完全明确。
我们使用扩散张量成像、组织病理学和免疫染色分析来证明内侧颞叶硬化症患者颞叶样本的正常细胞结构以及无异常情况。这些样本用于体外分离和富集胶质祖细胞,随后在体内检测此类细胞。
我们在正常成人大脑白质中鉴定出一个SOX2+细胞亚群,其中大多数与OLIG2共定位。这些细胞可以在体外分离和富集,在体外它们会增殖并产生未成熟(O4+)和成熟(MBP+)少突胶质细胞,在较小程度上还会产生星形胶质细胞(GFAP+)。
我们的结果证明在正常成人大脑白质中存在一个表达SOX2的新的胶质祖细胞亚群。这些细胞可能对组织再生程序有用。