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

Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
Sarika SaraswatiPampee P Young

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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Citations

Feb 11, 2016·Advances in Wound Care·Alexander J WhittamGeoffrey C Gurtner
Dec 30, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Beibei ZhaiZhengfeng Yin
Jan 13, 2015·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Lucia FormigliSandra Zecchi-Orlandini
Nov 2, 2013·World Journal of Stem Cells·Eunhyun ChoiKi-Chul Hwang
Aug 14, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dikshya BastakotyPampee P Young
Sep 18, 2020·The Biochemical Journal·Peter G ChildsMatthew J Dalby
Jul 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zonggui WangChangqing Zuo

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