Schwindt Telma T, Motta Fabiana L, Gabriela F Barnabé, Cristina G Massant, Guimarães Alessander O, Calcagnotto Maria Elisa, Pesquero João B, Mello Luiz E
Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
An Acad Bras Cienc. 2009 Sep;81(3):443-52. doi: 10.1590/s0001-37652009000300009.
Cell therapy for neurological disorders has advanced, and neural precursor cells (NPC) may become the ideal candidates for neural transplantation in a wide range of diseases. However, additional work has to be done to determine either the ideal culture environment for NPC expansion in vitro, without altering their plasticity, or the FGF-2 and EGF mechanisms of cell signaling in neurospheres growth, survival and differentiation. In this work we evaluated mouse neurospheres cultured with and without FGF-2 and EGF containing medium and showed that those growth factors are responsible for NPC proliferation. It is also demonstrated that endogenous production of growth factors shifts from FGF-2 to IGF-1/PDGFb upon EGF and FGF-2 withdrawal. Mouse NPC cultured in suspension showed different patterns of neuronal localization (core versus shell) for both EGF and FGF-2 withdrawal and control groups. Taken together, these results show that EGF and FGF-2 removal play an important role in NPC differentiation and may contribute to a better understanding of mechanisms of NPC differentiation. Our findings suggest that depriving NPC of growth factors prior to grafting might enhance their chance to effectively integrate into the host.
用于神经疾病的细胞疗法已经取得进展，神经前体细胞（NPC）可能成为多种疾病神经移植的理想候选者。然而，仍需开展更多工作，以确定在不改变其可塑性的情况下，用于NPC体外扩增的理想培养环境，或者确定神经球生长、存活和分化过程中FGF-2和EGF的细胞信号传导机制。在这项研究中，我们评估了在含有和不含FGF-2及EGF的培养基中培养的小鼠神经球，结果表明这些生长因子负责NPC的增殖。研究还表明，在撤除EGF和FGF-2后，生长因子的内源性产生从FGF-2转变为IGF-1/PDGFb。悬浮培养的小鼠NPC在撤除EGF和FGF-2的组以及对照组中均显示出不同的神经元定位模式（核心与外壳）。综上所述，这些结果表明，撤除EGF和FGF-2在NPC分化中起重要作用，可能有助于更好地理解NPC分化机制。我们的研究结果表明，在移植前剥夺NPC的生长因子可能会增加它们有效整合到宿主中的机会。
