1. Hyaluronic acid ameliorates the proliferative ability of human amniotic epithelial cells through activation of TGF-β/BMP signaling
- Author
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Nuo-Xin Wang, Yan Xu, Ru-Ming Liu, Yi Luo, Jian-Hui Xiao, Ya-Bing Tian, and Chang-Yin Yu
- Subjects
Homeobox protein NANOG ,Hyaluronic acid ,lcsh:Medicine ,Human amniotic epithelial cells ,General Biochemistry, Genetics and Molecular Biology ,Extracellular matrix ,Cell therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,030304 developmental biology ,0303 health sciences ,Pro-proliferation ,General Neuroscience ,lcsh:R ,Mesenchymal stem cell ,Cell Biology ,General Medicine ,In vitro ,Cell biology ,chemistry ,030220 oncology & carcinogenesis ,Amniotic epithelial cells ,cardiovascular system ,Stem cell ,General Agricultural and Biological Sciences ,TGF-β/BMP signaling pathway ,Translational Medicine - Abstract
Human amniotic epithelial cells (hAECs) are a useful and noncontroversial source of stem cells for cell therapy and regenerative medicine, but their limited proliferative ability hinders the acquisition of adequate quantities of cells for clinical use due to not expressing telomerase in hAECs. Our previous study showed that hyaluronic acid (HA), an important component of the extracellular matrix, promoted the proliferation of human amniotic mesenchymal stem cells. Herein, we hypothesize that HA might improve the proliferative capability of hAECs. In the present study, the role of HA on the proliferation of human amniotic epithelial cells (hAECs) in vitro was investigated for the first time. HA at molecular weight of 300 kDa showed an obvious pro-proliferation effect on hAECs. Furthermore, HA not only kept phenotypic characteristics and differentiation capabilities of hAECs, but significantly promoted the secretion of the anti-inflammatory factors such as IL-10 and TGF-β1, and the expression of stem cell pluripotent factors such as Oct4 and Nanog. Analysis of PCR microarray data and RT-qPCR validation showed that TGF-β/BMP signaling was activated in the presence of HA. Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling, significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B, SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. These data suggest that HA is a safe and effective enhancer for in vitro expansion of hAECs, whose regulatory mechanism involves the TGF-β/BMP signaling.
- Published
- 2020