Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat
2007 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 6, 1257-1266 p.Article in journal (Refereed) Published
Aims/hypothesis: The few patients subjected to autotransplantation of pancreatic islets after pancreatectomy usually become normoglycaemic after using islets from the resected organ only, whereas allogeneic recipients usually require at least two grafts to retain normoglycaemia. Previous experimental studies have demonstrated that islets transplanted to non-pancreatectomised recipients acquire a markedly decreased blood vessel density, which leads to a hypoxic microenvironment. The aim of the present study was to test the hypothesis that autotransplanted islets have better vascular engraftment and function as a result of the pancreatic surgery involved. Materials and methods: In the present study, athymic mice and inbred rats were subjected to a 60% pancreatectomy and transplanted with human or rat islets, respectively, 4 days later. Control animals underwent sham surgery. Blood flow, oxygen tension, vascular density and endocrine volume in the islet grafts were measured 1 month after transplantation. Separate grafts were used for perfusion experiments and for assessment of beta cell proliferation and endocrine cellular apoptosis at different time periods after transplantation. Results: Islet grafts in partially pancreatectomised recipients had an increased blood flow, oxygen tension, blood vessel density and endocrine mass 1 month post-transplantation compared with control animals. They also exhibited increased insulin release in perfusion experiments performed 1 month post-transplantation, and decreased cellular apoptosis early after transplantation. Conclusions/interpretation: The present study shows that the pancreatectomy procedure itself has beneficial effects on the engraftment of transplanted human and rat islets. Our results provide an additional explanation, besides diminished immunological responses, of the much better outcome of islet autotransplantations compared with allogeneic transplantations in the clinic.
Place, publisher, year, edition, pages
2007. Vol. 50, no 6, 1257-1266 p.
Blood flow, Insulin release, Islet graft, Islet transplantation, Oxygen tension, Revascularisation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-94338DOI: 10.1007/s00125-007-0649-5ISI: 000246271600019PubMedID: 17406853OAI: oai:DiVA.org:uu-94338DiVA: diva2:168156