Tissue Eng Regen Med.  2017 Oct;14(5):595-604. 10.1007/s13770-017-0068-8.

Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells

Affiliations
  • 1Department of Urology, School of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju 38066, Korea.
  • 2BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea.
  • 3Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea. urokbs@knu.ac.kr, tgkwon@knu.ac.kr
  • 4Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 Hyunchung-ro, Nam-gu, Daegu 42415, Korea.
  • 5Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan 44667, Korea.
  • 6Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu 42415, Korea.

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.

Keyword

Hypoxia; Mesenchymal stem cells; Stem cell property; Stem cell niche; Normoxia

MeSH Terms

Aging
Amniotic Fluid
Anoxia*
Cell Culture Techniques
Cell Proliferation
Dental Pulp
Female
Gene Expression
Humans*
Mesenchymal Stromal Cells*
Nestin
Oxygen
Real-Time Polymerase Chain Reaction
Stem Cell Niche
Stem Cells
Oxygen
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