Formation of Cholangiogenic Cysts Following Intrahepatic Islet Transplantation in Streptozotocin Diabetic Rats.

Permanent hyperinsulinemia and the resulting overstimulation of the insulin receptor signaling pathway is suspected as a trigger of cancer genesis in the livers of type 2 diabetic patients. Liver tissue (LT) surrounding transplanted pancreatic islets (PI) can be permanently exposed to insulin in even higher concentrations than in type 2 diabetic patients. Therefore, this study examines the effect of PI transplantation (Tx) on LT in animals with streptozotocin (STZ)-induced diabetes mellitus. The suboptimal mass (400 or 1000) of isogeneic PI was transplanted into either the portal vein or under the kidney capsule of diabetic Brown Norway (BN) rats. Healthy BN rats treated with 400 isogeneic PI transplanted in the portal vein served as a control group. During the first 6 months after PI Tx, small and infrequent cystic lesions developed in animals with STZ diabetes, irrespective of the Tx site. In 10 months, frequent and complex cystic lesions appeared in these animals. In the control group, several small lesions were detected but not until 10 months after the PI Tx. In summary, STZ is the likely main inductor of hepatic cystic lesions, but the contribution of PI was not confirmed.

In vivo vascularization of anisotropic channeled porous polylactide-based capsules for islet transplantation: the effects of scaffold architecture and implantation site.

The replacement of pancreatic islets for the possible treatment of type 1 diabetes is limited by the extremely high oxygen demand of the islets. To this end, here we hypothesize to create a novel extra-hepatic highly-vascularized bioartificial cavity using a porous scaffold as a template and using the host body as a living bioreactor for subsequent islet transplantation. Polylactide-based capsular-shaped anisotropic channeled porous scaffolds were prepared by following the unidirectional thermally-induced phase separation technique, and were implanted under the skin and in the greater omentum of Brown Norway rats. Polyamide mesh-based isotropic regular porous capsules were used as the controls. After 4weeks, the implants were excised and analyzed by histology. The hematoxylin and eosin, as well as Masson's trichrome staining, revealed a) low or no infiltration of giant inflammatory cells in the implant, b) minor but insignificant fibrosis around the implant, c) guided infiltration of host cells in the test capsule in contrast to random cell infiltration in the control capsule, and d) relatively superior cell infiltration in the capsules implanted in the greater omentum than in the capsules implanted under the skin. Furthermore, the anti-CD31 immunohistochemistry staining revealed numerous vessels at the implant site, but mostly on the external surface of the capsules. Taken together, the current study, the first of its kind, is a significant step-forward towards engineering a bioartificial microenvironment for the transplantation of islets.

Effect of mesenchymal stem cells on the vascularization of the artificial site for islet transplantation in rats.

An adequate vascularization of the artificially created cavity is crucial for subsequent transplantation of isolated pancreatic islets. In a reported study, dynamic contrast-enhanced magnetic resonance imaging was used to assess the effect of mesenchymal stem cells on neoangiogenesis within connective tissue surrounding an implantable biocompatible device. The signal increase detected after injection of magnetic resonance contrast agent in each target region was considered to be an effect of contrast agent, which was related to the blood supply. To minimize the influence of variability in contrast agent application, all outcomes measured in the implanted devices were normalized to the signal intensity of kidney tissue. When supported by mesenchymal stem cells, the mean signal increase intra-abdominally was 42%, 41%, and 64% and within subcutaneously implanted devices was 23%, 54%, and 52% of that measured in kidney.

Gene expression changes in rat pancreas transplant model after long-term cold storage of the graft in perfluorohexyloctane.

BACKGROUND: Perfluorohexyloctane (PFH) is a promising storage solution that has been successfully used for pancreas preservation before islet isolation. This hyperoxygen carrier has been designed to prevent ischemic injury to the pancreas graft during cold storage. In our storage, we aimed to evaluate the impact of this solution on long-term cold storage in a rat whole pancreas transplantation model. METHOD: Brown-Norway rats were used for syngeneic heterotopic pancreas transplantation. The procured organs were cold-stored for 18 hours in preoxygenated PFH (PFH group; n = 8) or in the University of Wisconsin solution (UW group; n = 8), or were transplanted immediately in the control group (n = 8). Two hours after reperfusion, we obtained blood and pancreas tissue samples for biochemistry and gene analyses (real-time polymerase chain reaction). RESULTS: A significant difference between the UW and PFH group was observed in the tumor necrosis factor (TNF)ß and endothelin 1 genes, which was overexpressed more than twofold in the UW group. In the blood samples, the UW group compared with the PFH group showed significantly higher levels of pancreatic amylase and lipase (94.2 ± 25.2 vs 67.7 ± 13.4 µkat/L and 5.5 ± 2.8 vs 3 ± 0.7 µkat/L, respectively; P < .05). CONCLUSION: We found significantly lower expression levels of the endothelin 1 and TNFß genes and lower concentrations of pancreatic amylase and lipase in the PFH group. All these findings suggest lower rate of ischemic reperfusion injury in the PFH group. These findings may result in better post-transplant outcomes after long-term cold storage in PFH compared with the UW solution. Further research in this area is required.