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

Acta Pharmacol Sin. 2018 Aug;39(8):1305-1316. doi: 10.1038/aps.2018.22. Epub 2018 Mar 22.

Abstract

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

MeSH terms

  • Amnion / cytology*
  • Animals
  • Carcinogenicity Tests
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cytokines / metabolism
  • Epithelial Cells* / physiology
  • Epithelial Cells* / transplantation
  • Female
  • Guinea Pigs
  • Humans
  • Male
  • Mice, Inbred ICR
  • Mice, Inbred NOD
  • Mice, SCID
  • Pregnancy
  • Primary Cell Culture
  • Radiation Injuries, Experimental / therapy
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*
  • Thy-1 Antigens / metabolism

Substances

  • Culture Media, Serum-Free
  • Cytokines
  • Thy-1 Antigens