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PLoS One. 2014 Jan 6;9(1):e83650. doi: 10.1371/journal.pone.0083650. eCollection 2014.

Drugging a stem cell compartment using Wnt3a protein as a therapeutic.

Author information

1
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California, United States of America.
2
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.
3
Departments of Structural Biology and Molecular and Cellular Physiology, Stanford School of Medicine, Stanford, California, United States of America.

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.

PMID:
24400074
PMCID:
PMC3882211
DOI:
10.1371/journal.pone.0083650
[Indexed for MEDLINE]
Free PMC Article
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