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

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

doi:10.1038/s41467-022-30103-2

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

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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 language	English (US)
Article number	2497
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30103-2
State	Published - Dec 2022
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-022-30103-2

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Takematsu, E., Massidda, M., Auster, J., Chen, P. C., Im, B. G., Srinath, S., Canga, S., Singh, A., Majid, M., Sherman, M., Dunn, A., Graham, A., Martin, P., & Baker, A. B. (2022). Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation. Nature communications, 13(1), Article 2497. https://doi.org/10.1038/s41467-022-30103-2

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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.",

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AU - Takematsu, Eri

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AU - Im, Byung Gee

AU - Srinath, Sanjana

AU - Canga, Sophia

AU - Singh, Aditya

AU - Majid, Marjan

AU - Sherman, Michael

AU - Dunn, Andrew

AU - Graham, Annette

AU - Martin, Patricia

AU - Baker, Aaron B.

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AB - 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.

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

Abstract

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