Center for Stem Cells and Medicine, Department of Cell Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Department of Histology and Embryology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Oxid Med Cell Longev. 2018 Feb 13;2018:7618704. doi: 10.1155/2018/7618704. eCollection 2018.
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% O) 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.
诱导性肝干细胞（iHepSCs）具有自我更新和双能分化特性，有望成为肝细胞治疗的供体细胞。然而，iHepSCs 的双分化效率和再殖效率相对较低。最近的证据表明，生理缺氧是干细胞“生态位”微环境中的一个重要因素，在调节组织干细胞的生物学行为，包括增殖和分化方面起着关键作用。在这项研究中，我们发现生理缺氧（10% O2）通过 p53-p21 信号通路加速 G1/S 期转变，增强了 iHepSCs 的干性特征，并促进了其增殖能力。此外，短期低氧预处理提高了 iHepSCs 肝向分化的效率，而长期低氧促进了胆管细胞分化，但抑制了 iHepSCs 的肝向分化。这些结果表明了缺氧对 iHepSCs 干性维持、增殖和双分化的潜在影响，为探索治疗性干细胞的合适培养条件提供了有前景的思路。
