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Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model

Authors

  • Yueh-Lun Lee,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • Lin-Wen Lee,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • Chen-Yao Su,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • George Hsiao,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • Yi-Yuan Yang,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • Sy-Jye Leu,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • Ying-Hua Shieh,

    1. Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    3. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    4. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    5. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    6. Research Department, Human Protein Process Science, Lille, France
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  • Thierry Burnouf

    Corresponding author
    1. Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
    2. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
    3. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    4. Department of Family Medicine, Taipei Medical University, Taipei, Taiwan
    5. Research Department, Human Protein Process Science, Lille, France
    • Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan
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  • This study was supported by the National Science Council of Taiwan through Grant NSC99-2314-B-038-002-MY3.

Address reprint requests to: Thierry Burnouf, PhD, College of Oral Medicine, Institute of Medical Biomaterial and Tissue Engineering, Taipei Medical University, Taipei 11031, Taiwan, e-mail: tburnou@attglobal.net.

Abstract

Background

Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-β1 (TGF-β1) content, PCLs may exert immunosuppressive and anti-inflammatory functions.

Study Design and Methods

PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-β in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-β1 was used as control.

Results

PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-β-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-β-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice.

Conclusion

S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates.

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