机构地区:[1]Institute of Genetics and Regenerative Biology, College of Life Sciences,Hangzhou 310058, China [2]College of Life Sciences-iCe# Biotechnology Regenerative Biomedicine Laboratory,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]Intemational 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
出 处:《Acta Pharmacologica Sinica》2018年第8期1305-1316,共12页中国药理学报(英文版)
基 金:This work was supported by the Project of Health Collaborative Innovation of Guangzhou City (Grant No 201704020214), the National Natural Science Foundation of China (Grant No 81770444 and 81600354) and Fundamental Research Funds for the Central Universities of China.
摘 要:Human amniotic epithelial cells (hAECs), derived from the innermost to be potential seed cells for allogeneic cell therapy. Previous studies ayer of the term placenta closest to the fetus, have been shown 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.Human amniotic epithelial cells (hAECs), derived from the innermost to be potential seed cells for allogeneic cell therapy. Previous studies ayer of the term placenta closest to the fetus, have been shown 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.
关 键 词:human amniotic epithelial cells cell therapy safety evaluation SERUM-FREE
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