Abstract
Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.
Highlights
Pancreatic islet transplantation has been considered along the last two decades as a promising therapy for beta-cell replacement in patients with type-1 diabetes
Diabetic nude mice were transplanted subcutaneously with islets embedded into a plasmabased scaffold without cells (PSI) or with fibroblasts (PSI-F)
We have observed that the use of a plasma-based scaffold alone (PSI) improved islet engraftment, reversed hyperglycemia and achieved short-term glycemic control, long-term control was only achieved when fibroblasts were included in the scaffold before transplantation (PSI-F)
Summary
Pancreatic islet transplantation has been considered along the last two decades as a promising therapy for beta-cell replacement in patients with type-1 diabetes. Most of islet recipients remained protected from recurrent hypoglycemia, less than 50% maintained insulin independence five years after islet transplantation [2, 3]. This long-term loss-of-function evidence the necessity of improving some aspects of islet transplantation, especially those addressing obstacles like engraftment and transplantation site [4]. Subcutaneous space stands out because of its accessibility and spaciousness, its poor vascularization constitutes its main limitation [9] Taking this in mind, improvement of angiogenesis becomes crucial for successful subcutaneous islet transplantation. Several attempts have been conducted, mainly focused on the use of different biomaterials as scaffolds, either alone or in combination with pro-angiogenic factors and, more recently, in combination with accessory cells with graft-supporting properties
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