Institute of Genetics and Regenerative Biology, College of Life Sciences, Hangzhou, 310058, Hangzhou, China.
College of Life Sciences-iCell, Biotechnology Regenerative Biomedicine Laboratory, Hangzhou, 310058, Hangzhou, China.
Acta Pharmacol Sin. 2018 Aug;39(8):1305-1316. doi: 10.1038/aps.2018.22. Epub 2018 Mar 22.
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.
人羊膜上皮细胞（hAECs）来源于胎盘最内层，与胎儿最接近的部位，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 hAECs 具有一定的治疗效果。然而，目前尚未开发出用于临床应用的 hAECs 合适的分离和培养系统。在本研究中，我们建立了一种无血清的 hAEC 分离和培养方案，与传统的含血清培养系统相比，观察到更好的细胞生长。除了细胞表面标志物（CD29、CD166 和 CD90）的特异性表达外，hAECs 的生物学特征分析表明其多能性标志物 SSEA4、OCT4 和 NANOG 的表达高于人间充质干细胞，而 HLA-DR 和 HLA-DQ 的表达水平非常低，提示 hAECs 的免疫原性较弱。有趣的是，CD90+ hAECs 被鉴定为具有强大免疫调节能力的独特群体。在系统安全性评估中，静脉注射 hAEC 不会导致溶血、过敏、毒性问题，更重要的是，不会导致致瘤性。最后，在辐射诱导损伤的小鼠中证实了 hAECs 的治疗效果。结果揭示了 hAECs 在全身损伤恢复中的新功能。因此，本研究为 hAEC 细胞治疗在临床应用中的管理提供了一种可行且安全的策略。
