Elvira Gema, García Isabel, Gallo Juan, Benito Marina, Montesinos Paula, Holgado-Martin Esther, Ayuso-Sacido Angel, Penadés Soledad, Desco Manuel, Silva Augusto, Garcia-Sanz Jose A
Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
Laboratory of Glyconanotechnology, CICbiomaGUNE, San Sebastian, Spain; CIBER-BBN, San Sebastian, Spain.
Stem Cell Res. 2015 Jan;14(1):114-29. doi: 10.1016/j.scr.2014.11.006. Epub 2015 Jan 3.
Neuroblasts represent the predominant migrating cell type in the adult mouse brain. There are, however, increasing evidences of migration of other neural precursors. This work aims at identifying in vivo endogenous early neural precursors, different from neuroblasts, able to migrate in response to brain injuries. The monoclonal antibody Nilo1, which unequivocally identifies type B astrocytes and embryonic radial glia, was coupled to magnetic glyconanoparticles (mGNPs). Here we show that Nilo1-mGNPs in combination with magnetic resonance imaging in living mice allowed the in vivo identification of endogenous type B astrocytes at their niche, as well as their migration to the lesion site in response to glioblastoma, demyelination, cryolesion or mechanical injuries. In addition, Nilo1(+) adult radial glia-like structures were identified at the lesion site a few hours after damage. For all damage models used, type B astrocyte migration was fast and orderly. Identification of Nilo1(+) cells surrounding an induced glioblastoma was also possible after intraperitoneal injection of the antibody. This opens up the possibility of an early identification of the initial damage site(s) after brain insults, by the migration of type B astrocytes.
神经母细胞是成年小鼠大脑中主要的迁移细胞类型。然而，越来越多的证据表明其他神经前体细胞也会发生迁移。这项研究旨在鉴定出与神经母细胞不同的、能够在脑损伤后发生迁移的体内内源性早期神经前体细胞。单克隆抗体Nilo1能够明确识别B型星形胶质细胞和胚胎期放射状胶质细胞，将其与磁性糖纳米颗粒（mGNPs）偶联。在此我们表明，在活体小鼠中，Nilo1-mGNPs与磁共振成像相结合能够在体内识别处于其生态位的内源性B型星形胶质细胞，以及它们对胶质母细胞瘤、脱髓鞘、冷冻损伤或机械损伤做出反应后向损伤部位的迁移。此外，在损伤后数小时，在损伤部位鉴定出了Nilo1(+)成年放射状胶质细胞样结构。对于所有使用的损伤模型，B型星形胶质细胞的迁移快速且有序。腹腔注射该抗体后，也能够鉴定出诱导性胶质母细胞瘤周围的Nilo1(+)细胞。这为通过B型星形胶质细胞的迁移早期识别脑损伤后的初始损伤部位提供了可能性。
