title: Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs).
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.
authors.affiliation: Department of Pathology, Vanderbilt Orthopaedic Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sarika
authors.initials: S
authors.lastname: Saraswati
authors.forename: Desirae L
authors.initials: DL
authors.lastname: Deskins
authors.forename: Ginger E
authors.initials: GE
authors.lastname: Holt
authors.forename: Pampee P
authors.initials: PP
authors.lastname: Young
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006097:Granulation Tissue / Q000187:drug effects* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011774:Pyrvinium Compounds / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects*; D051176:beta Catenin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011774:Pyrvinium Compounds; D051153:Wnt Proteins; D051176:beta Catenin; C024631:pyrvinium