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Drugging a stem cell compartment using Wnt3a protein as a therapeutic.
- Source :
-
PloS one [PLoS One] 2014 Jan 06; Vol. 9 (1), pp. e83650. Date of Electronic Publication: 2014 Jan 06 (Print Publication: 2014). - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Bone Marrow Cells drug effects
Bone Marrow Cells metabolism
Carrier Proteins metabolism
Cell Survival drug effects
Cholic Acids pharmacology
Dose-Response Relationship, Drug
Humans
Hydrophobic and Hydrophilic Interactions
Lipids pharmacology
Liposomes chemistry
Liposomes metabolism
Mice
Protein Binding
Protein Conformation drug effects
Protein Stability
Recombinant Proteins chemistry
Recombinant Proteins pharmacology
Thermodynamics
Wnt Signaling Pathway drug effects
Wnt3A Protein chemistry
Stem Cells drug effects
Stem Cells metabolism
Wnt3A Protein metabolism
Wnt3A Protein pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24400074
- Full Text :
- https://doi.org/10.1371/journal.pone.0083650