PT  - JOURNAL ARTICLE
AU  - Eri Takematsu
AU  - Jeff Auster
AU  - Po-Chih Chen
AU  - Sanjana Srinath
AU  - Sophia Canga
AU  - Aditya Singh
AU  - Marjan Majid
AU  - Michael Sherman
AU  - Andrew Dunn
AU  - Annette Graham
AU  - Patricia Martin
AU  - Aaron B. Baker
TI  - Transmembrane Stem Cell Factor Protein Therapeutics Enhance Revascularization in Ischemia without Mast Cell Activation
AID  - 10.1101/2020.04.06.028563
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.06.028563
4099  - http://biorxiv.org/content/early/2020/04/07/2020.04.06.028563.short
4100  - http://biorxiv.org/content/early/2020/04/07/2020.04.06.028563.full
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.