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

Author

Listed:
  • 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
    University of Texas at Austin
    University of Texas at Austin
    University of Texas at Austin)

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.

Suggested Citation

  • 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 Mar, 2022. "Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30103-2
    DOI: 10.1038/s41467-022-30103-2
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    References listed on IDEAS

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    1. Rob Phillips & Tristan Ursell & Paul Wiggins & Pierre Sens, 2009. "Emerging roles for lipids in shaping membrane-protein function," Nature, Nature, vol. 459(7245), pages 379-385, May.
    2. Lei Ding & Thomas L. Saunders & Grigori Enikolopov & Sean J. Morrison, 2012. "Endothelial and perivascular cells maintain haematopoietic stem cells," Nature, Nature, vol. 481(7382), pages 457-462, January.
    3. Hiroshi Suzuki & Yukiko Kurihara & Motohiro Takeya & Nobuo Kamada & Motoyukl Kataoka & Kouichi Jishage & Otoya Ueda & Hisashl Sakaguchi & Takayuki Higashi & Tsukasa Suzuki & Yoshiaki Takashima & Yoshi, 1997. "A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection," Nature, Nature, vol. 386(6622), pages 292-296, March.
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