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Bone tissue engineering with bone marrow-derived stromal cells integrated with concentrated growth factor in Rattus norvegicus calvaria defect model

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Abstract

Concentrated growth factor (CGF) is an autologous leukocyte-rich and platelet-rich fibrin (L-PRF) biomaterial termed “second-generation platelet concentrate”. CGF contains autologous osteoinductive platelet growth factors and an osteoconductive fibrin matrix. The purpose of this study was to assess the ability of CGF combined with bone marrow stromal cells (BMSCs) to heal critical-size rat calvaria defects in vivo and to modulate the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. In the in-vivo study, the CGF group regenerated bone better than the control group, and combined therapy with CGF and BMSCs almost completely repaired critical-size bone defects within 12 weeks after surgery. In the in-vitro study, the CGF extract, at concentrations between 1 and 10 %, promoted proliferation, osteogenic maturation, and mineralization of hTERT-E6/E7 human MSCs in a dose-dependent manner but had an inhibitory effect at higher concentrations. In conclusion, a CGF extract promoted the proliferation, osteogenic maturation, and mineralization of mesenchymal stem cells in vitro, and combination therapy with CGF and BMSCs resulted in excellent healing of critical-size bone defects in vivo.

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Acknowledgments

We thank Dr Junya Toguchida, Kyoto University, for kindly providing the hTERT-E6/E7 cells and Mrs Mari Shinkawa for technical assistance with the histological study. This study was supported by a Grant-in-Aid for Scientific Research (no. 23390364) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and by a special research subsidy from Terumo Life Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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No competing financial interests exist.

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Authors and Affiliations

  1. Medical Center for Translational and Clinical Research, Department of Medical Innovation, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hirotsugu Honda & Akira Myoui

  2. Department of Orthopaedics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Noriyuki Tamai, Norifumi Naka & Hideki Yoshikawa

Authors
  1. Hirotsugu Honda
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  2. Noriyuki Tamai
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  3. Norifumi Naka
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  4. Hideki Yoshikawa
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  5. Akira Myoui
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Correspondence to Akira Myoui.

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Honda, H., Tamai, N., Naka, N. et al. Bone tissue engineering with bone marrow-derived stromal cells integrated with concentrated growth factor in Rattus norvegicus calvaria defect model. J Artif Organs 16, 305–315 (2013). https://doi.org/10.1007/s10047-013-0711-7

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  • DOI: https://doi.org/10.1007/s10047-013-0711-7

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