Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs)

Authors

  • Sarika Saraswati PhD,

    1. Department of Pathology, Vanderbilt Orthopaedic Institute, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Desirae L. Deskins BA,

    1. Department of Pathology, Vanderbilt Orthopaedic Institute, Vanderbilt University Medical Center, Nashville, TN, USA
    2. The Department of Veterans Affairs Medical Center, Nashville, TN, USA
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  • Ginger E. Holt MD,

    1. Department of Orthopaedics and Rehabilitation, Vanderbilt Orthopaedic Institute, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Pampee P. Young MD, PhD

    Corresponding author
    1. Department of Internal Medicine, Vanderbilt Orthopaedic Institute, Vanderbilt University Medical Center, Nashville, TN, USA
    2. The Department of Veterans Affairs Medical Center, Nashville, TN, USA
    • Department of Pathology, Vanderbilt Orthopaedic Institute, Vanderbilt University Medical Center, Nashville, TN, USA
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Reprint requests:

Dr. P. Young, Vanderbilt University School of Medicine, Department of Pathology, 1161 21st Avenue South C2217A MCN, Nashville, TN 37232, USA.

Tel: 615 936 1098;

Fax: 615 343 7023;

Email: pampee.young@vanderbilt.edu

Abstract

We and others have found that Wnt signaling inhibition is important in mesenchymal stem cell (MSC) self-renewal. Pyrvinium was identified as a potent Wnt inhibitor in a chemical screen for small molecules. In the present study, we hypothesized that pyrvinium will enhance MSC self-renewal to improve the clinical efficacy of MSC therapy. Pyrvinium increased MSC proliferation in vitro while inhibiting their osteogenic and chondrogenic lineage commitment by reducing cytoplasmic β-catenin. Although MSCs are a promising target for cell therapy, strategies to enhance their survival and maintain their stemness in the wounded area are essential. Using an in vivo model of granulation tissue formation, we demonstrated that pyrvinium enhanced long-term MSC engraftment. Pyrvinium-treated MSC-generated granulation tissue also demonstrated less ectopic differentiation into bone or cartilage. This study highlights the potential of using a therapeutic Wnt inhibitor to enhance MSC-driven regenerative therapy.

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