Human amniotic epithelial cells (hAECs), derived from the innermost layer of the term placenta closest to the fetus, have been shown to be potential seed cells for allogeneic cell therapy. Previous studies have shown a certain therapeutic effect of hAECs. However, no appropriate isolation and culture system for hAECs has been developed for clinical applications. In the present study, we established a serum-free protocol for hAEC isolation and cultivation, in which better cell growth was observed compared with that in a traditional culture system with serum. In addition to specific expression of cell surface markers (CD29, CD166 and CD90), characterization of the biological features of hAECs revealed expression of the pluripotent markers SSEA4, OCT4 and NANOG, which was greater than that in human mesenchymal stem cells, whereas very low levels of HLA-DR and HLA-DQ were detected, suggesting the weak immunogenicity of hAECs. Intriguingly, CD90+ hAECs were identified as a unique population with a powerful immunoregulatory capacity. In a systemic safety evaluation, intravenous administration of hAEC did not result in hemolytic, allergy, toxicity issues or, more importantly, tumorigenicity. Finally, the therapeutic effect of hAECs was demonstrated in mice with radiation-induced damage. The results revealed a novel function of hAECs in systemic injury recovery. Therefore, the current study provides an applicable and safe strategy for hAEC cell therapy administration in the clinical setting.

中文翻译：

---

无血清系统中人羊膜上皮细胞的生物学特性及其安全性评估。

人类羊膜上皮细胞（hAECs）起源于最接近胎儿的术语胎盘最内层，已被证明是同种异体细胞治疗的潜在种子细胞。先前的研究表明，hAEC具有一定的治疗作用。但是，尚未为临床应用开发适用于hAEC的合适的分离和培养系统。在本研究中，我们建立了用于hAEC分离和培养的无血清方案，与传统的含血清培养系统相比，该方案观察到更好的细胞生长。除了特异性表达细胞表面标志物（CD29，CD166和CD90）以外，对hAECs生物学特性的表征还揭示了多能性标志物SSEA4，OCT4和NANOG的表达，其表达高于人间充质干细胞，而检测到的HLA-DR和HLA-DQ含量非常低，表明hAEC的免疫原性较弱。有趣的是，CD90 + hAEC被鉴定为具有强大免疫调节能力的独特人群。在系统安全性评估中，静脉内注射hAEC不会导致溶血，过敏，毒性问题或更重要的是致瘤性。最后，hAECs的治疗作用在辐射诱发的损伤小鼠中得到证实。结果揭示了hAEC在系统性损伤恢复中的新功能。因此，本研究为临床环境中的hAEC细胞疗法管理提供了一种适用且安全的策略。CD90 + hAEC被鉴定为具有强大免疫调节能力的独特人群。在系统安全性评估中，静脉内注射hAEC不会导致溶血，过敏，毒性问题或更重要的是致瘤性。最后，hAECs的治疗作用在辐射诱发的损伤小鼠中得到证实。结果揭示了hAEC在系统性损伤恢复中的新功能。因此，本研究为临床环境中的hAEC细胞疗法管理提供了一种适用且安全的策略。CD90 + hAEC被鉴定为具有强大免疫调节能力的独特人群。在系统安全性评估中，静脉内注射hAEC不会导致溶血，过敏，毒性问题或更重要的是致瘤性。最后，hAECs的治疗作用在辐射诱发的损伤小鼠中得到证实。结果揭示了hAEC在系统性损伤恢复中的新功能。因此，本研究为临床环境中的hAEC细胞疗法管理提供了一种适用且安全的策略。结果揭示了hAEC在系统性损伤恢复中的新功能。因此，本研究为临床环境中的hAEC细胞疗法管理提供了一种适用且安全的策略。结果揭示了hAEC在系统性损伤恢复中的新功能。因此，本研究为临床环境中的hAEC细胞疗法管理提供了一种适用且安全的策略。