FGF8 activates proliferation and migration in mouse post-natal oligodendrocyte progenitor cells.

FGF8 activates proliferation and migration in mouse post-natal oligodendrocyte progenitor cells.
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DOI:
10.1371/journal.pone.0108241
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Jones J
Jones J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cruz-Martinez P;Martinez-Ferre A;Jaramillo-Merchán J;Estirado A;Martinez S;Jones J

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成纤维细胞生长因子8 (Fibroblast growth factor 8, FGF8)是中枢神经系统早期胚胎发育所必需的关键分子信号,但在此之后迅速消失。众所周知,它是小脑、端脑和痉挛组织者等结构中细胞命运和存活过程所需的主要形态发生信号之一,而它的缺失会导致神经系统严重异常,胚胎通常在发育的早期阶段死亡。在这项工作中,我们已经观察到该因子在脱髓鞘疾病,如白质营养不良或多发性硬化症中的新的可能的治疗作用。在体外,用分化培养基和FGF8培养少突胶质细胞祖细胞。通过免疫细胞化学和PCR进行分化和增殖研究。此外,在基质培养中进行了迁移研究,将少突胶质细胞祖细胞放置在fgf8浸泡的肝素珠的一定距离上。结果表明,FGF8对细胞迁移和增殖均有诱导作用。此外,在体内脱髓鞘小鼠模型中也观察到类似的效果,其中观察到少突胶质祖细胞向fgf8浸泡的肝素珠迁移,并将其移植到肝素珠中。综上所述,本研究结果表明FGF8是体外诱导少突胶质细胞祖细胞活化、迁移和增殖的新因子,可在脱髓鞘动物模型中进行体内外推。
Fibroblast growth factor 8 (FGF8) is a key molecular signal that is necessary for early embryonic development of the central nervous system, quickly disappearing past this point. It is known to be one of the primary morphogenetic signals required for cell fate and survival processes in structures such as the cerebellum, telencephalic and isthmic organizers, while its absence causes severe abnormalities in the nervous system and the embryo usually dies in early stages of development. In this work, we have observed a new possible therapeutic role for this factor in demyelinating disorders, such as leukodystrophy or multiple sclerosis. In vitro, oligodendrocyte progenitor cells were cultured with differentiating medium and in the presence of FGF8. Differentiation and proliferation studies were performed by immunocytochemistry and PCR. Also, migration studies were performed in matrigel cultures, where oligodendrocyte progenitor cells were placed at a certain distance of a FGF8-soaked heparin bead. The results showed that both migration and proliferation was induced by FGF8. Furthermore, a similar effect was observed in an in vivo demyelinating mouse model, where oligodendrocyte progenitor cells were observed migrating towards the FGF8-soaked heparin beads where they were grafted. In conclusion, the results shown here demonstrate that FGF8 is a novel factor to induce oligodendrocyte progenitor cell activation, migration and proliferation in vitro, which can be extrapolated in vivo in demyelinated animal models.
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