Although the sites for clinical or experimental islet transplantation have been well established, the pancreatic islet survival and function in homing locations still remain unsatisfied. One of possible reasons that account for this is local hypoxia due to shortage of blood supply. Here we modified a prevascularized tissue engineering chamber in vivo which facilitated the vitality and function of seeded islets by providing a microvascular network prior to transplantation. Three hundreds of syngenic islets were seeded into the Matrigel^TM-filled chamber on the day of implanting chamber in the groin of streptozotocin-induced diabetic mice (day 0), or into the chamber of 14 days or 28 days prevascularization, or 300, 200, 100 syngenic islets were seeded into the chamber of 28 days prevascularization, respectively. The lengths that blood glucose levels of diabetic mice were reduced to normoglycemia are closely correlated with the days of prevascularization and the number of inserted islets. Furthermore, because xenotransplantation of pancreatic islets is a potential solution for type I diabetes mellitus, we transplanted 1000 human islets into the chamber of 28 days prevascularizion and treated the diabetic mice with monoclonal antibody regimens. Treated with anti-CD45RB alone, the mice failed to accept xenografts eventually (n = 6, MST = 46.3 ± 13.8 days). However, after the diabetic mice were treated with combination of anti-CD45RB and anti-CD40L (MR1), the MST of islet xenografts was prolongated and 1 of 7 was induced to long-term survival (n = 7, MST > 64 days), which was not significantly different with the human islet survival under kidney capsule of mice treated with anti-CD45RB (n = 8, MST > 71 days, p > 0.05). In conclusion, these findings highlight that the novel prevascularized construct could serve as an alternative site for pancreatic islet transplantation, implicating a potentially clinical application in the future.

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