title: Drugging a stem cell compartment using Wnt3a protein as a therapeutic.
abstract: The therapeutic potential of Wnt proteins has long been recognized but challenges associated with in vivo stability and delivery have hindered their development as drug candidates. By exploiting the hydrophobic nature of the protein we provide evidence that exogenous Wnt3a can be delivered in vivo if it is associated with a lipid vesicle. Recombinant Wnt3a associates with the external surface of the lipid membrane; this association stabilizes the protein and leads to prolonged activation of the Wnt pathway in primary cells. We demonstrate the consequences of Wnt pathway activation in vivo using a bone marrow engraftment assay. These data provide validation for the development of WNT3A as a therapeutic protein.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Girija R
authors.initials: GR
authors.lastname: Dhamdhere
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Fang
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Lee
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Du
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Olveda
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Developmental Biology, Howard Hughes Medical Institute (HHMI), Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Mulligan
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Carlson
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Ransom
authors.affiliation: Departments of Structural Biology and Molecular and Cellular Physiology, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002793:Cholic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D013816:Thermodynamics; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D002793:Cholic Acids; D008055:Lipids; D008081:Liposomes; D011994:Recombinant Proteins; D060509:Wnt3A Protein; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate