Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cell Biol Int. 2021 Jan;45(1):140-153. doi: 10.1002/cbin.11478. Epub 2020 Dec 1.
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.
人类子宫内膜干细胞（hEnSCs）可以分化为多种神经细胞类型，被认为是神经组织工程和再生医学的合适细胞群体。考虑到激素、生长因子和其他因素在神经系统中相互作用的不同，已经提出了几种分化方案来指导 hEnSCs 向特定的神经细胞分化。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，首次基于神经基因和蛋白质的表达水平，研究了 17β-雌二醇（雌激素，E2）对 hEnSCs 神经分化的影响。为此，在没有或存在 17β-雌二醇的情况下，将 hEnSCs 暴露于维甲酸（RA）、表皮生长因子（EGF）和碱性成纤维细胞生长因子-2（FGF2）中，使其分化为类神经元细胞。大多数细胞呈多极形态。在所有组中，巢蛋白、Tuj-1 和 NF-H（神经丝重链）（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，在雌激素处理组中，神经元特异性标志物的表达更高。这些发现表明，17β-雌二醇与其他生长因子一起可以刺激和上调 hEnSCs 神经元分化过程中神经标志物的表达。此外，我们的研究结果证实，hEnSCs 可以作为神经退行性疾病细胞治疗和神经组织工程的合适细胞来源。
