Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression

Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression
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DOI:
10.1016/s0014-4886(03)00133-x
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发表时间:
2003-11-01
影响因子:
5.3
通讯作者:
Greenberg, DA
Greenberg, DA
中科院分区:
医学2区
文献类型:
--
作者:
Jin, KL;Mao, XO;Greenberg, DA

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骨髓细胞(BMC)可以在体外被诱导表达神经元表型特征,但它们转分化为成熟的功能性神经元的程度尚不确定。我们研究了不同生长因子及其组合对富含骨髓基质细胞的 BMC 培养物中神经元标记蛋白表达的影响。神经元标记物表达模式根据 BMC 培养物所接触的生长因子或多种因子而变化。用表皮生长因子、成纤维细胞生长因子-2、视黄酸和神经生长因子处理长达 5 周的培养物显示出神经元样细胞过程并表达神经元标记物,包括神经元核抗原 NeuN、微管相关蛋白 2、tau、突触素、α(1A) 和 α(1B) 钙通道亚基、NR2A 谷氨酸受体亚基和 γ-氨基丁酸酸。然而,这些标记物的细胞内分布与它们在成熟神经元中的通常分布不同。我们得出的结论是,多种生长因子可以驱动 BMC 向一种或多种神经元表型发展,但神经元的形态特征以及神经元蛋白和神经递质的异位表达可能并不等同于执行正常神经元功能的能力。 (C) 2003 年爱思唯尔科学(美国)。版权所有。
Bone marrow cells (BMC) can be induced to express neuronal phenotypic features in vitro, but the extent to which they can transdifferentiate to mature, functional neurons is uncertain. We examined the effects of different growth factors and combinations thereof on the expression of neuronal marker proteins in cultures of BMC enriched in marrow stromal cells. Patterns of neuronal marker expression varied depending on the growth factor or factors to which BMC cultures were exposed. Cultures treated for up to 5 weeks with epidermal growth factor, fibroblast growth factor-2, retinoic acid, and nerve growth factor displayed neuron-like cellular processes and expressed neuronal markers, including the neuronal nuclear antigen NeuN, microtubule-associated protein 2, tau, synaptophysin, alpha(1A) and alpha(1B) calcium channel subunits, NR2A glutamate receptor subunits, and gamma-aminobutyric acid. However, the intracellular distribution of these markers was distinct from their usual distribution in mature neurons. We conclude that a variety of growth factors can drive BMC toward a neuronal phenotype or phenotypes, but that morphological neuronal features and the ectopic expression of neuronal proteins and neurotransmitters may not equate with the ability to execute normal neuronal functions. (C) 2003 Elsevier Science (USA). All rights reserved.