Human endometrial stem cells (hEnSCs) that can be differentiated into various neural cell types have been regarded as a suitable cell population for neural tissue engineering and regenerative medicine. Considering different interactions between hormones, growth factors, and other factors in the neural system, several differentiation protocols have been proposed to direct hEnSCs towards specific neural cells. The 17β‐estradiol plays important roles in the processes of development, maturation, and function of nervous system. In the present research, the impact of 17β‐estradiol (estrogen, E2) on the neural differentiation of hEnSCs was examined for the first time, based on the expression levels of neural genes and proteins. In this regard, hEnSCs were differentiated into neuron‐like cells after exposure to retinoic acid (RA), epidermal growth factor (EGF), and also fibroblast growth factor‐2 (FGF2) in the absence or presence of 17β‐estradiol. The majority of cells showed a multipolar morphology. In all groups, the expression levels of nestin, Tuj‐1 and NF‐H (neurofilament heavy polypeptide) (as neural‐specific markers) increased during 14 days. According to the outcomes of immunofluorescence (IF) and real‐time PCR analyses, the neuron‐specific markers were more expressed in the estrogen‐treated groups, in comparison with the estrogen‐free ones. These findings suggest that 17β‐estradiol along with other growth factors can stimulate and upregulate the expression of neural markers during the neuronal differentiation of hEnSCs. Moreover, our findings confirm that hEnSCs can be an appropriate cell source for cell therapy of neurodegenerative diseases and neural tissue engineering.

中文翻译：

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定义 17β-雌二醇在人子宫内膜干细胞向神经元样细胞分化中的作用

可以分化为各种神经细胞类型的人类子宫内膜干细胞 (hEnSCs) 被认为是神经组织工程和再生医学的合适细胞群。考虑到神经系统中激素、生长因子和其他因素之间的不同相互作用，已经提出了几种分化方案来将 hEnSCs 导向特定的神经细胞。17β-雌二醇在神经系统的发育、成熟和功能过程中起着重要作用。在本研究中，基于神经基因和蛋白质的表达水平，首次研究了 17β-雌二醇（雌激素，E2）对 hEnSCs 神经分化的影响。在这方面，hEnSCs 在暴露于视黄酸（RA）后分化为神经元样细胞，表皮生长因子 (EGF) 和成纤维细胞生长因子 2 (FGF2) 在 17β-雌二醇不存在或存在的情况下。大多数细胞呈现多极形态。在所有组中，巢蛋白、Tuj-1 和 NF-H（神经丝重多肽）（作为神经特异性标志物）的表达水平在 14 天内增加。根据免疫荧光 (IF) 和实时 PCR 分析的结果，与不含雌激素的组相比，雌激素治疗组的神经元特异性标志物表达更多。这些发现表明 17β-雌二醇和其他生长因子可以在 hEnSCs 的神经元分化过程中刺激和上调神经标志物的表达。而且，