title: Liposomal packaging generates Wnt protein with in vivo biological activity.
abstract: Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University, Stanford, California, United States of America.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Morrell
authors.forename: Philipp
authors.initials: P
authors.lastname: Leucht
authors.forename: Ludan
authors.initials: L
authors.lastname: Zhao
authors.forename: Jae-Beom
authors.initials: JB
authors.lastname: Kim
authors.forename: Derk
authors.initials: D
authors.lastname: ten Berge
authors.forename: Karthik
authors.initials: K
authors.lastname: Ponnusamy
authors.forename: A Lyonel
authors.initials: AL
authors.lastname: Carre
authors.forename: Henryk
authors.initials: H
authors.lastname: Dudek
authors.forename: Marie
authors.initials: M
authors.lastname: Zachlederova
authors.forename: Michael
authors.initials: M
authors.lastname: McElhaney
authors.forename: Shirley
authors.initials: S
authors.lastname: Brunton
authors.forename: Janet
authors.initials: J
authors.lastname: Gunzner
authors.forename: Marinella
authors.initials: M
authors.lastname: Callow
authors.forename: Paul
authors.initials: P
authors.lastname: Polakis
authors.forename: Mike
authors.initials: M
authors.lastname: Costa
authors.forename: Xiaoyan M
authors.initials: XM
authors.lastname: Zhang
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D008081:Liposomes; D008297:Male; D008563:Membrane Lipids / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D008081:Liposomes; D008563:Membrane Lipids; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse