Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37§

Authors

  • Anna Krasnodembskaya,

    1. The Cardiovascular Research Institute, University of California San Francisco, San Francisco, California
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  • Yuanlin Song,

    1. Department of Anesthesiology University of California San Francisco, San Francisco, California
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  • Xiaohui Fang,

    1. The Cardiovascular Research Institute, University of California San Francisco, San Francisco, California
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  • Naveen Gupta,

    1. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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  • Vladimir Serikov,

    1. Children's Hospital Research Institute, Children's Hospital Oakland Research Institute, Oakland, California
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  • Jae-Woo Lee,

    1. The Cardiovascular Research Institute, University of California San Francisco, San Francisco, California
    2. Department of Anesthesiology University of California San Francisco, San Francisco, California
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  • Michael A. Matthay

    Corresponding author
    1. The Cardiovascular Research Institute, University of California San Francisco, San Francisco, California
    2. Department of Anesthesiology University of California San Francisco, San Francisco, California
    3. Department of Medicine, University of California San Francisco, San Francisco, California
    • Cardiovascular Research Institute, University of California San Francisco, 505 Parnassus Ave., Box 0130, San Francisco, CA 94143, USA
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    • Telephone: 415-476-1079; Fax: 415-502-2126;


  • Author contributions: A.K.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; Y.S.: conception and design, collection and/or assembly of data, data analysis and interpretation; X.F.: conception and design, collection and/or assembly of data, data analysis and interpretation; N.G.: conception and design, financial support; V.S.: conception and design, collection and/or assembly of data; J.L.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; M.A.M.: conception and design, financial and administrative support, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • First published online in STEM CELLS EXPRESS October 13, 2010.

  • §

    Disclosure of potential conflicts of interest is found at the end of this article.

Abstract

Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E.coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/ LL-37. STEM CELLS 2010;28:2229–2238

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