Hypoxia Upregulates Mitotic Cyclins Which Contribute to the Multipotency of Human Mesenchymal Stem Cells by Expanding Proliferation Lifespan

  • Lee, Janet (Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Hyun-Soo (Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Su-Min (Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Dong-Ik (Department of Vascular Surgery, Samsung Seoul Hospital, Sungkyunkwan University School of Medicine) ;
  • Lee, Chang-Woo (Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2017.09.22
  • Accepted : 2017.12.26
  • Published : 2018.03.31


Hypoxic culture is widely recognized as a method to efficiently expand human mesenchymal stem cells (MSCs) without loss of stem cell properties. However, the molecular basis of how hypoxia priming benefits MSC expansion remains unclear. In this report, our systemic quantitative proteomic and RT-PCR analyses revealed the involvement of hypoxic conditioning activated genes in the signaling process of the mitotic cell cycle. Introduction of screened two mitotic cyclins, CCNA2 and CCNB1, significantly extended the proliferation lifespan of MSCs in normoxic condition. Our results provide important molecular evidence that multipotency of human MSCs by hypoxic conditioning is determined by the mitotic cell cycle duration. Thus, the activation of mitotic cyclins could be a potential strategy to the application of stem cell therapy.


Supported by : National Research Foundation


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