Abstract
The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear.The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures.MSCs were both able to prolong the survival of pancreatic islets, and to directly differentiate into an “insulin-releasing” phenotype. Two distinct mechanisms mediated these effects: i) the survival increase was observed in pancreatic islets indirectly co-cultured with MSCs, probably mediated by the trophic factors released by MSCs; ii) MSCs in direct contact with pancreatic islets started to express Pdx1, a pivotal gene of insulin production, and then differentiated into insulin releasing cells. These results demonstrate that MSCs may be useful for potentiating pancreatic islets' functionality and feasibility.
Highlights
The transplantation of pancreatic islets currently represents a promising therapeutic option for the management of insulindependent diabetes, being an alternative both to the standard therapeutic approach with insulin injections, and to complete pancreas transplantation that has been proposed [1]
In order to improve the feasibility of islet transplantation for the treatment of diabetes, it has been proposed to associate pancreatic islets with Mesenchymal Stem Cells (MSCs), a population of adult stem cells initially identified in bone marrow and found in other tissues such as adipose tissue, skin, and amniotic fluid [4]
Most of the MSCs directly added to pancreatic islets (500,000 cells/flask) adhered to the bottom of the flask, where they took the particular fibroblastic-like form already described [6], while a few of these cells adhered to floating pancreatic islets
Summary
The transplantation of pancreatic islets currently represents a promising therapeutic option for the management of insulindependent diabetes, being an alternative both to the standard therapeutic approach with insulin injections, and to complete pancreas transplantation that has been proposed [1]. MSCs are harvestable from patients, with high plasticity [5], immunomodulatory properties [6], and with the ability to support cellular survival both through direct contact [7,8] and by the release of trophic factors [9,10]. By means of these particular features it can be surmised that MSCs may improve the survival of pancreatic islets and, the success of the transplantation [11,12,13]
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