Characterization of time-course morphological features for efficient prediction of osteogenic potential in human mesenchymal stem cells

Authors

  • Fumiko Matsuoka,

    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Aichi, Japan
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    • Fumiko Matsuoka and Ichiro Takeuchi contributed equally to this work.
  • Ichiro Takeuchi,

    1. Department of Engineering, Nagoya Institute of Technology, Showa-ku, Nagoya, Aichi, Japan
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    • Fumiko Matsuoka and Ichiro Takeuchi contributed equally to this work.
  • Hideki Agata,

    1. Tissue Engineering Research Group, Division of Molecular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan
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  • Hideaki Kagami,

    1. Tissue Engineering Research Group, Division of Molecular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan
    2. Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry, Hirooka, Shiojiri, Japan
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  • Hirofumi Shiono,

    1. Nikon Corporation, Chiyoda-ku, Tokyo, Japan
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  • Yasujiro Kiyota,

    1. Nikon Corporation, Chiyoda-ku, Tokyo, Japan
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  • Hiroyuki Honda,

    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Aichi, Japan
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  • Ryuji Kato

    Corresponding author
    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Aichi, Japan
    2. Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa-ku, Nagoya, Aichi, Japan
    • Correspondence to: R. Kato

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  • This article was published online on 30 January 2014. Subsequently, it was determined that the article contained an earlier version of Figure 4, and the correct version was published on 21 February 2014

ABSTRACT

Human bone marrow mesenchymal stem cells (hBMSCs) represents one of the most frequently applied cell sources for clinical bone regeneration. To achieve the greatest therapeutic effect, it is crucial to evaluate the osteogenic differentiation potential of the stem cells during their culture before the implantation. However, the practical evaluation of stem cell osteogenicity has been limited to invasive biological marker analysis that only enables assaying a single end-point. To innovate around invasive quality assessments in clinical cell therapy, we previously explored and demonstrated the positive predictive value of using time-course images taken during differentiation culture for hBMSC bone differentiation potential. This initial method establishes proof of concept for a morphology-based cell evaluation approach, but reveals a practical limitation when considering the need to handle large amounts of image data. In this report, we aimed to scale-down our proposed method into a more practical, efficient modeling scheme that can be more broadly implemented by physicians on the frontiers of clinical cell therapy. We investigated which morphological features are critical during the osteogenic differentiation period to assure the performance of prediction models with reduced burden on image acquisition. To our knowledge, this is the first detailed characterization that describes both the critical observation period and the critical number of time-points needed for morphological features to adequately model osteogenic potential. Our results revealed three important observations: (i) the morphological features from the first 3 days of differentiation are sufficiently informative to predict bone differentiation potential, both activities of alkaline phosphatase and calcium deposition, after 3 weeks of continuous culture; (ii) intervals of 48 h are sufficient for measuring critical morphological features; and (iii) morphological features are most accurately predictive when early morphological features from the first 3 days of differentiation are combined with later features (after 10 days of differentiation). Biotechnol. Bioeng. 2014;111: 1430–1439. © 2014 Wiley Periodicals, Inc.

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