Biological characterization of human amniotic epithelial cells in a serum-free system and their safety evaluation

Peng-jie YANG1,2,3, Wei-xin YUAN1,2,3, Jia LIU4, Jin-ying LI1,2,3, Bing TAN1,2,3, Chen QIU1,2,3, Xiao-long ZHU1,2,3, Cong QIU1,2,3, Dong-mei Lai5, Li-he GUO6,7, Lu-yang YU1,2,3
1 Institute of Genetics and Regenerative Biology, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
2 College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Zhejiang University, Hangzhou 310058, China
3 Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
4 Life Science College, Zhejiang Chinese Medical University, Hangzhou 310053, China
5 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
6 Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
7 Shanghai iCELL Biotechnology Co Ltd, Shanghai 200333, China
Correspondence to: Lu-yang YU:,
DOI: 10.1038/aps.2018.22
Received: 25 November 2017
Accepted: 1 January 2018
Advance online: 22 March 2018


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.
Keywords: human amniotic epithelial cells; cell therapy; safety evaluation; serum-free

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