Transmembrane Stem Factor Nanodiscs Enhanced Revascularization in a Hind Limb Ischemia Model in Diabetic, Hyperlipidemic Rabbits.

Autor:	Takematsu E; The University of Texas at Austin., Massidda M; The University of Texas at Austin., Howe G; The University of Texas Health Science Center at Houston., Goldman J; The University of Texas Health Science Center at Houston., Felli P; The University of Texas Health Science Center at Houston., Mei L; The University of Texas at Austin., Callahan G; The University of Texas at Austin., Sligar A; The University of Texas at Austin., Smalling R; The University of Texas Health Science Center at Houston., Baker A; The University of Texas at Austin.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Jun 16. Date of Electronic Publication: 2023 Jun 16.
DOI:	10.21203/rs.3.rs-2997323/v1
Abstrakt:	Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia. Competing Interests: Competing interests The authors (ET and ABB) have patented the technology presented in this manuscript. The other authors (MM, GH, JG, PF, LM, GC, ADS, and RS) on the study do not have competing interests.
Databáze:	MEDLINE
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