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.
Highlights
Transplantation of insulin-producing cells, such as the islets of Langerhans, is a promising treatment for type 1 diabetes
Since the skin is less vascularized than the native pancreas, vascularization of the subcutaneous implanted scaffold is imperative for transplantation outcomes and efficacy [15]
To determine the effect of H2S on vascularization of subcutaneous scaffolds, they were implanted in C57BL/6 mice for 63 days and processed for reverse transcription polymerase chain reaction (RT-PCR) and histology of vascularization markers
Summary
Transplantation of insulin-producing cells, such as the islets of Langerhans, is a promising treatment for type 1 diabetes It provides continuous regulation of the blood glucose levels and results in stable glycemic control and the reduction of secondary complications such as cardiovascular diseases, retinopathy, and nephropathy. Since the human body does not provide a better islet transplantation site, engineering an artificial islet transplantation site, called a scaffold, that mimics the pancreatic microenvironment, could be a solution [3]. Such a scaffold could be implanted under the skin, making transplantation of insulin-producing cells only a minor surgical procedure and allowing for retrieval of these cells. Retrievability might be mandatory with replenishable cell sources, like stem cells, that still have some insufficiencies such as incomplete maturation, uncontrolled proliferation, aberrant protein expression, and tumorigenic potential [4]
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