The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice

Abstract

Islet transplantation into subcutaneous polymer scaffolds has shown to successfully induce normoglycemia in type 1 diabetes models. Vascularization of these scaffolds is imperative for optimal control of glucose levels. We studied the effect of the vascular stimulator hydrogen sulfide (H2S) on the degree of vascularization of a scaffold and the role of the immune system in this process. Scaffolds were subcutaneously implanted in immunocompetent C57BL/6 and immunocompromised nude mice. Mice received twice-daily intraperitoneal injections of the fast-releasing H2S donor sodium hydrosulfide (NaHS, 25 or 50 μmol/kg) or saline for 28 days. After 63 days the vascular network was analyzed by histology and gene expression. Here we showed that the vascularization of a subcutaneous scaffold in nude mice was significantly impaired by H2S treatment. Both the CD31 gene and protein expression were reduced in these scaffolds compared to the saline-treated controls. In C57BL/6 mice, the opposite was found, the vascularization of the scaffold was significantly increased by H2S. The mRNA expression of the angiogenesis marker CD105 was significantly increased compared to the controls as well as the number of CD31 positive blood vessels. In conclusion, the immune system plays an important role in the H2S mediated effect on vascularization of subcutaneous scaffolds.

Gasotransmitter-Induced Therapeutic Angiogenesis: A Biomaterial Prospective

“…The immunocompromised mice had compromised vasculature and angiogenesis, whereas vascularization in the immunocompetent mice showed a significant increase, indicating the role of the immune system in H 2 S-mediated angiogenesis . As per the report, T cells are involved in the H 2 S-mediated angiogenesis with the fact that H 2 S activates DNA methylation of Foxp3 T regulatory cells to promote immune tolerance,which can induce anti-inflammatory responses …”

“…95 As per the report, T cells are involved in the H 2 S-mediated angiogenesis with the fact that H 2 S activates DNA methylation of Foxp3 T regulatory cells to promote immune tolerance,which can induce anti-inflammatory responses. 96 3.4.2. Fibrous Membranes.…”

H2S Protects Against Immobilization-Induced Muscle Atrophy via Reducing Oxidative Stress and Inflammation

“…The chosen doses of GYY4137 ( Huang et al, 2021 ) and NaHS ( Smink et al, 2020 ) were based on previous studies and our preliminary experiments showing that GYY4137 and NaHS at the doses of 50 mg/kg and 20 μmol/kg were well tolerated in mice and significantly attenuated immobilization-induced muscle atrophy. Especially, in our preliminary experiments it was determined that the NAHS at the dose of 20 μmol/kg had a better protective effect than 50 μmol/kg in maintaining muscle mass and decreasing muscle atrophy related genes expressions ( Supplementary Figure S1 ).…”

Role of hydrogen sulphide in physiological and pathological angiogenesis

“…The fast‐releasing H 2 S donor, NaHS (25 or 50 μmol/kg), is intraperitoneally injected into the nude mice implanted with subcutaneous scaffolds. After 63 days, the mRNA expression of angiogenesis marker CD105 and the number of CD31 positive vessels are significantly higher than those in the control group, indicating that H 2 S can promote vascularization of subcutaneous scaffolds 181 . However, the release of H 2 S by NaHS is fast and difficult to control, which is prone to cause cytotoxicity due to high local concentration.…”

“…After 63 days, the mRNA expression of angiogenesis marker CD105 and the number of CD31 positive vessels are significantly higher than those in the control group, indicating that H 2 S can promote vascularization of subcutaneous scaffolds. 181 However, the release of H 2 S by NaHS is fast and difficult to control, which is prone to cause cytotoxicity due to high local concentration. To solve this problem, a microparticle system (NaHS@MPs) encapsulated NaHS has been designed.…”