Background: Although islet transplantation successful applied, shortage of donors, poor islet survival and toxicity of immunosuppressants often reduce the graft functional lifetime. Tissue engineered scaffold constructed with porcine small intestinal submucosa (SIS) is a novel effective solution. We previously showed that SIS promote the recovery and subsequent function of islets, but cannot improve the graft revascularization. A large number of researches demonstrated co-transplantation of islets with mesenchymal stem cells (MSCs) can improve graft outcome, which has been attributed to the effects of MSCs on revascularization and preservation. Hence, in the present study, we construct artificial pancreas using SIS coated MSCs and islets to investigate whether it could improve graft function and revascularization.

Methods: Rat islets with or without bone marrow MSCs coated in SIS to construct artificial pancreas. The viability of islets was tested by AO/PI staining. Its function was assessed by measuring glucose-stimulated insulin secretion in vitro. The artificial pancreases were transplanted into diabetic rats, and blood glucose concentrations were monitored. Grafts were recovered3 weeks after transplantation, and then islets function and vascularisation were determined by immunohistochemical.

Results: In vitro, when co-cultured with MSCs, the mRNA of PDX-1 specific markers in islets was increased (P<0.05), Islet yield (300±20IEQ) and islet viability (93±2.1%) were significantly higher than control group (246±18IEQ,87±1.9%, respectively; P<0.05), which indicated that MSCs is important for islet survival. Islets with MSCs coated in SIS had increased glucose-stimulated insulin secretion from and content (P<0.01). However, there was no neovascularisation process observed in the short time. In vivo, both of the groups leaded to glucose control. MSCs and islets groups was observed superior than only islets coated in SIS for improving islet graft survival time significantly form 6.1±1.24 to 26.6±2.81 days. For blood glucose levels and vascularization, it was confirmed that islets with MSCs coated in SIS also improved graft function.

Conclusions: Our results have suggested that MSCs were enhanced revascularization and improved the efficacy of coated islets in SIS. The artificial pancreas may offer a new approach for curing diabetes.

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