Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation

Eri Takematsu, Miles Massidda, Jeff Auster, Po-Chih Chen, ByungGee Im, Sanjana Srinath, Sophia Canga, Aditya Singh, Marjan Majid, Michael Sherman, Andrew Dunn, Annette Graham, Patricia Martin and Aaron B. Baker ()
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Eri Takematsu: University of Texas at Austin
Miles Massidda: University of Texas at Austin
Jeff Auster: University of Texas at Austin
Po-Chih Chen: University of Texas at Austin
ByungGee Im: University of Texas at Austin
Sanjana Srinath: University of Texas at Austin
Sophia Canga: University of Texas at Austin
Aditya Singh: University of Texas at Austin
Marjan Majid: University of Texas at Austin
Michael Sherman: University of Texas Medical Branch
Andrew Dunn: University of Texas at Austin
Annette Graham: Glasgow Caledonian University
Patricia Martin: Glasgow Caledonian University
Aaron B. Baker: University of Texas at Austin

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-30103-2

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