Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 05 2022
06 05 2022
Historique:
received:
28
03
2020
accepted:
08
04
2022
entrez:
6
5
2022
pubmed:
7
5
2022
medline:
11
5
2022
Statut:
epublish
Résumé
Stem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects.
Identifiants
pubmed: 35523773
doi: 10.1038/s41467-022-30103-2
pii: 10.1038/s41467-022-30103-2
pmc: PMC9076913
doi:
Substances chimiques
Lipids
0
Membrane Proteins
0
Stem Cell Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2497Informations de copyright
© 2022. The Author(s).
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