RT Journal Article
SR Electronic
T1 Transmembrane Stem Cell Factor Protein Therapeutics Enhance Revascularization in Ischemia without Mast Cell Activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.06.028563
DO 10.1101/2020.04.06.028563
A1 Eri Takematsu
A1 Jeff Auster
A1 Po-Chih Chen
A1 Sanjana Srinath
A1 Sophia Canga
A1 Aditya Singh
A1 Marjan Majid
A1 Michael Sherman
A1 Andrew Dunn
A1 Annette Graham
A1 Patricia Martin
A1 Aaron B. Baker
YR 2020
UL http://biorxiv.org/content/early/2020/04/07/2020.04.06.028563.abstract
AB 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.