Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex
Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex
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DOI：
10.1093/brain/awm200
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发表时间：
2007-11-01
期刊：
影响因子：
14.5
通讯作者：
Kiss, Jozsef Z.
中科院分区：
文献类型：
--
作者：
Dayer, Alexandre G.;Jenny, Benoit;Kiss, Jozsef Z.
增强移植的干细胞/祖细胞在出生后大脑中产生多潜能、增殖和迁移细胞池的能力的策略对于脑损伤后的结构修复至关重要。我们研究了神经祖细胞（NPCs）中碱性成纤维细胞生长因子2 （FGF-2）的过度表达是否可以为大鼠大脑皮层组织修复的NPCs迁移提供一个强大的来源。通过实时成像，我们提供了直接证据，证明FGF-2过表达显著增强了移植npc在复杂3D结构（如皮质切片）中的迁移能力。此外，我们发现过表达FGF-2的npc在体内移植后仍保持迁移和增殖特性。重要的是，在移植到新生儿缺血皮质后，FGF-2过表达的npc有效地侵入受损皮质，并产生更多的未成熟神经元池，可用于大脑修复。祖细胞向未成熟神经元的分化与FGF-2转基因的逐渐下调有关。这些结果揭示了FGF-2在与宿主组织相互作用时调节npc功能的重要作用，并提供了一种潜在的策略，可以产生强大的迁移和未成熟祖细胞来源，用于修复新生儿缺血皮质。
Strategies to enhance the capacity of grafted stem/progenitors cells to generate multipotential, proliferative and migrating pools of cells in the postnatal brain could be crucial for structural repair after brain damage. We investigated whether the over-expression of basic fibroblast growth factor 2 (FGF-2) in neural progenitor cells (NPCs) could provide a robust source of migrating NPCs for tissue repair in the rat cerebral cortex. Using live imaging we provide direct evidence that FGF-2 over-expression significantly enhances the migratory capacity of grafted NPCs in complex 3D structures, such as cortical slices. Furthermore, we show that the migratory as well as proliferative properties of FGF-2 over-expressing NPCs are maintained after in vivo transplantation. Importantly, after transplantation into a neonatal ischaemic cortex, FGF-2 over-expressing NPCs efficiently invade the injured cortex and generate an increased pool of immature neurons available for brain repair. Differentiation of progenitor cells into immature neurons was correlated with a gradual down-regulation of the FGF-2 transgene. These results reveal an important role for FGF-2 in regulating NPCs functions when interacting with the host tissue and offer a potential strategy to generate a robust source of migrating and immature progenitors for repairing a neonatal ischaemic cortex.