Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation
Year: 2022
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, American Heart Association, Japan Student Services Organization, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Biomedical Imaging and Bioengineering, Congressionally Directed Medical Research Programs
Awards: G1323018493, G1919330366, G21146293, G4119534169, G4275087904, Glycocalyx Mimetic Polysaccharides as Therapeutics for Atherosclerosis, FLEXIBLE REGENERATIVE NANOELECTRONICS FOR ADVANCED PERIPHERAL NEURAL INTERFACES, G5576383394, G5850682332, G5973062423, Nanodisc Therapeutics for Peripheral ischemia in Diabetes, Development of an Advanced Injectable Therapy for Ischemic Vascular Disease, Flexible Regenerative Nanoelectronics for Advanced Peripheral Neural Interfaces, DEVELOPMENT OF AN ADVANCED INJECTABLE THERAPY FOR ISCHEMIC VASCULAR DISEASE, Mechanical Conditioning of Mesenchymal Stem Cells for Enhanced Recellularized Vascular Grafts, G7836306403, Syndecan-1 in Mechanosensing of Engineered Microenvironments, G8350580235, G8417524994, G9000138960, G972172960
OpenAlex ID: W4229015697