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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 06, 2022
- Source ID
- 10.1038/s41467-022-30103-2
Entities
People
- Aaron B Baker
- Aditya Singh
- Andrew Dunn
- Annette Graham
- Byunggee Im
- Eri Takematsu
- Jeff Auster
- Marjan Majid
- Michael Sherman
- Miles W. Massidda
- Patricia Martin
- Po-chih Chen
- Sanjana Srinath
- Sophia Canga
Organizations
- American Heart Association
- Congressionally Directed Medical Research Programs
- National Heart, Lung, and Blood Institute
- National Institute of Biomedical Imaging and Bioengineering
- United States Department of Health and Human Services