@article{71a3a1a43b1846a9b730c6c4f39a2135,
title = "Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation",
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.",
author = "Eri Takematsu and Miles Massidda and Jeff Auster and Chen, {Po Chih} and Im, {Byung Gee} and Sanjana Srinath and Sophia Canga and Aditya Singh and Marjan Majid and Michael Sherman and Andrew Dunn and Annette Graham and Patricia Martin and Baker, {Aaron B.}",
note = "Funding Information: The authors gratefully acknowledge funding through the American Heart Association (17IRG33410888), the DOD CDMRP (W81XWH-16-1-0580; W81XWH-16-1-0582), and the National Institutes of Health (1R21EB023551-01; 1R21EB024147-01A1; 1R01HL141761-01) to A.B.B. The authors gratefully acknowledge funding through the Japan Student Services Organization to ET (L15126080002). We thank Sebastian Greenhough for the collection and processing of tissue via the GCU Skin Tissue bank, supported by a grant from Animal Free Research (A.G.), and who did not participate in any experiments involving animals or animal tissue. Funding Information: The authors gratefully acknowledge funding through the American Heart Association (17IRG33410888), the DOD CDMRP (W81XWH-16-1-0580; W81XWH-16-1-0582), and the National Institutes of Health (1R21EB023551-01; 1R21EB024147-01A1; 1R01HL141761-01) to A.B.B. The authors gratefully acknowledge funding through the Japan Student Services Organization to ET (L15126080002). We thank Sebastian Greenhough for the collection and processing of tissue via the GCU Skin Tissue bank, supported by a grant from Animal Free Research (A.G.), and who did not participate in any experiments involving animals or animal tissue. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-30103-2",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}