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Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Atmospheric (in vitro) oxygen pressure is around 150 mm Hg (20% O2), whereas physiologic (in vivo) oxygen pressure ranges between 5 and 50 mm Hg (0.7–7% O2). The normoxic environment in cell culture does not refer to a physiological stem cell niche. The aim of this study is to investigate the effect of oxygen concentration on cell properties of human mesenchymal stem cells (MSCs). We analyzed cell proliferation rate, senescence, immunophenotype, stemness gene expression and differentiation potency with human urine stem cells (USCs), dental pulp stem cells (DPSCs), amniotic fluid stem cells (AFSCs), and bone marrow stromal cells (BMSCs). USCs, DPSCs, AFSCs and BMSCs were cultured under either 5% O2 hypoxic or 20% O2 normoxic conditions for 5 days. MSCs cultured under hypoxia showed significantly increased proliferation rate and high percentage of S-phase cells, compared to normoxic condition. In real-time PCR assay, the cells cultured under hypoxia expressed higher level of Oct4, C-Myc, Nanog, Nestin and HIF-1α. In immunophenotype analysis, MSCs cultured under hypoxia maintained higher level of the MSC surface markers, and lower hematopoietic markers. Senescence was inhibited under hypoxia. Hypoxia enhances osteogenic differentiation efficiency compared to normoxia. Hypoxia showed enhanced cell proliferation rate, retention of stem cell properties, inhibition of senescence, and increased differentiation ability compared to normoxia.

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Acknowledgements

This work was supported by Biomedical Research Institute Grant, Kyungpook National University Hospital (2014).

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Author notes

  1. Se Yun Kwon and So Young Chun have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, School of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, 38066, Korea

    Se Yun Kwon

  2. BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Korea

    So Young Chun

  3. Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Korea

    Yun-Sok Ha, Hyun Tae Kim, Eun Sang Yoo, Bum Soo Kim & Tae Gyun Kwon

  4. Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 Hyunchung-ro, Nam-gu, Daegu, 42415, Korea

    Dae Hwan Kim

  5. Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan, 44667, Korea

    Jeongshik Kim

  6. Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu, 42415, Korea

    Phil Hyun Song

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  1. Se Yun Kwon
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Correspondence to Bum Soo Kim or Tae Gyun Kwon.

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The authors declare that they have no Conflict of interest.

Ethical statement

This study was approved by the Ethics Committee of the Kyungpook National University Hospital (IRB No. KNUH 2012-10-018).

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Kwon, S.Y., Chun, S.Y., Ha, YS. et al. Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells. Tissue Eng Regen Med 14, 595–604 (2017). https://doi.org/10.1007/s13770-017-0068-8

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  • DOI: https://doi.org/10.1007/s13770-017-0068-8

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