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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 7618704, 10 pages
Research Article

Physiological Hypoxia Enhances Stemness Preservation, Proliferation, and Bidifferentiation of Induced Hepatic Stem Cells

1Center for Stem Cells and Medicine, Department of Cell Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China
2Department of Histology and Embryology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China
3The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China
4Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine & Health Sciences, 279th Zhouzhu Road, Shanghai 201318, China

Correspondence should be addressed to Jian Zhao; moc.621@dx_jz, Xiaoyuan Zi; moc.361@nauyoaix_iz, and Yi-Ping Hu; nc.ude.umms@uhpy

Received 10 October 2017; Accepted 24 December 2017; Published 13 February 2018

Academic Editor: Pablo Muriel

Copyright © 2018 Xiaosong Zhi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their self-renewal and bipotential differentiation properties. However, the efficiency of bidifferentiation and repopulation efficiency of iHepSCs is relatively low. Recent evidence shows that physiological hypoxia, a vital factor within stem cell “niche” microenvironment, plays key roles in regulating tissue stem cell biological behaviors including proliferation and differentiation. In this study, we found that physiological hypoxia (10% O2) enhanced the stemness properties and promoted the proliferation ability of iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway. In addition, short-term hypoxia preconditioning improved the efficiency of hepatic differentiation of iHepSCs, and long-term hypoxia promoted cholangiocytic differentiation but inhibited hepatic differentiation of iHepSCs. These results demonstrated the potential effects of hypoxia on stemness preservation, proliferation, and bidifferentiation of iHepSCs and promising perspective to explore appropriate culture conditions for therapeutic stem cells.