Chromosomal variability of human mesenchymal stem cells cultured under hypoxic conditions

Hanae Ueyama, Tomohisa Horibe, Shiro Hinotsu, Tomoaki Tanaka, Takeomi Inoue, Hisashi Urushihara, Akira Kitagawa, Koji Kawakami

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Bone marrow derived human mesenchymal stem cells (hMSCs) have attracted great interest from both bench and clinical researchers because of their pluripotency and ease of expansionex vivo. However, these cells do finally reach a senescent stage and lose their multipotent potential. Proliferation of these cells is limited up to the time of their senescence, which limits their supply, and they may accumulate chromosomal changes throughex vivoculturing. The safe, rapid expansion of hMSCs is critical for their clinical application. Chromosomal aberration is known as one of the hallmarks of human cancer, and therefore it is important to understand the chromosomal stability and variability ofex vivoexpanded hMSCs before they are used widely in clinical applications. In this study, we examined the effects of culturing under ambient (20%) or physiologic (5%) O 2 concentrations on the rate of cell proliferation and on the spontaneous transformation of hMSCs in primary culture and after expansion, because it has been reported that culturing under hypoxic conditions accelerates the propagation of hMSCs. Bone marrow samples were collected from 40 patients involved in clinical research. We found that hypoxic conditions promote cell proliferation more favourably than normoxic conditions. Chromosomal aberrations, including structural instability or aneuploidy, were detected in significantly earlier passages under hypoxic conditions than under normoxic culture conditions, suggesting that amplification of hMSCs in a low-oxygen environment facilitated chromosomal instability. Furthermore, smoothed hazard-function modelling of chromosomal aberrations showed increased hazard after the fourth passage under both sets of culture conditions, and showed a tendency to increase the detection rate of primary karyotypic abnormalities among donors aged 60 years and over. In conclusion, we propose that the continuous monitoring of hMSCs will be required before they are used in therapeutic applications in the clinic, especially when cells are cultured under hypoxic conditions.

Original languageEnglish
Pages (from-to)72-82
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

Keywords

  • Bone marrow derived mesenchymal stem cells
  • Chromosomal aberration
  • Hypoxia
  • Karyotype
  • Regenerative medicine

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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  • Cite this

    Ueyama, H., Horibe, T., Hinotsu, S., Tanaka, T., Inoue, T., Urushihara, H., Kitagawa, A., & Kawakami, K. (2012). Chromosomal variability of human mesenchymal stem cells cultured under hypoxic conditions. Journal of Cellular and Molecular Medicine, 16(1), 72-82. https://doi.org/10.1111/j.1582-4934.2011.01303.x