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首页> 外文期刊>Journal of Neuroscience Methods >Retinoid supplementation of differentiating human neural progenitors and embryonic stem cells leads to enhanced neurogenesis in vitro.
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Retinoid supplementation of differentiating human neural progenitors and embryonic stem cells leads to enhanced neurogenesis in vitro.

机译：分化人类神经祖细胞和胚胎干细胞的类维生素A补充导致体外神经发生增强。

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摘要

Retinoids are important molecules involved in the development and homeostasis of the nervous system. As such, various retinoid derivatives are often found in culture media and supplement formulations to support the growth and maintenance of neural cells. However, all-trans-retinoic acid (ATRA) and its associated derivatives are light sensitive and are highly susceptible to isomerisation. This can lead to variability in retinoid concentrations and the nature of the retinoid species present in culture solutions which in turn can influence biological activity and introduce inconsistency. We have previously described the development of the synthetic retinoid derivative, EC23, as a chemically and light stable alternative that does not degrade and has biological activity similar to ATRA. In this study we demonstrate that the addition of exogenous retinoid can significantly enhance neuronal differentiation of both human neuroprogenitor and human embryonic stem cells. In the former, both ATRA and EC23 induced increased maturation and stabilisation of the axonal cytoskeleton. However, EC23 was particularly potent at lower nanomolar concentrations resulting in significantly greater neurogenesis than ATRA. In ES cells enhanced motor neuron marker expression was also detected in response to both retinoids when incorporated into an established protocol for neuronal differentiation. We propose that synthetic retinoid EC23 represents a valuable addition to the formulation of new and existing culture supplements to enhance neuronal differentiation whilst enabling improved consistency.
机译：类维生素A是涉及神经系统发育和体内稳态的重要分子。因此，通常在培养基和补充制剂中发现各种类维生素A衍生物以支持神经细胞的生长和维持。但是，全反式维甲酸（ATRA）及其相关衍生物对光敏感，并且高度易异构化。这可能导致类维生素A浓度的变化以及培养液中存在的类维生素A种类的性质，进而影响生物活性并导致不一致。先前我们已经描述了合成类视黄醇衍生物EC23的开发，它是一种化学性质和光稳定性的替代品，不会降解并且具有类似于ATRA的生物活性。在这项研究中，我们证明外源类视黄醇的添加可以显着增强人类神经祖细胞和人类胚胎干细胞的神经元分化。在前者中，ATRA和EC23均可诱导轴突细胞骨架的成熟和稳定。但是，EC23在较低的纳摩尔浓度下特别有效，导致神经发生作用明显大于ATRA。在ES细胞中，当纳入为神经元分化建立的协议中时，还响应于两种类维生素A检测到增强的运动神经元标记表达。我们建议合成类维生素A EC23代表新的和现有的文化补品配方的宝贵补充，以增强神经元分化，同时提高一致性。

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