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Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells ( MSCs )
Author(s) -
Saraswati Sarika,
Deskins Desirae L.,
Holt Ginger E.,
Young Pampee P.
Publication year - 2012
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2012.00767.x
Subject(s) - mesenchymal stem cell , wnt signaling pathway , chondrogenesis , granulation tissue , microbiology and biotechnology , in vivo , stem cell , progenitor cell , regeneration (biology) , cancer research , medicine , immunology , biology , signal transduction , wound healing
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.