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

Eri Takematsu , Miles Massidda, Jeff Auster, Po-Chih Chen, Byunygee Im, Sanjana Srinath, Sophia Canga, Aditya Singh, Marjan Majid, Michael Sherman, Andrew Dunn, Annette Graham, Patricia Martin, Aaron B. Baker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article number2497
Number of pages13
JournalNature Communications
Volume13
DOIs
Publication statusPublished - 6 May 2022

Keywords

  • angiogenesis
  • biomedical engineering
  • drug discovery

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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