Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat.
OBJECTIVE
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.


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
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.
Johansson
M
M
Department of Medical Cell Biology, Uppsala University, Husargatan 3, Box 571, 751 23 Uppsala, Sweden.
Jansson
L
L
Carlsson
P-O
PO
D000328:Adult; D000818:Animals; D001783:Blood Flow Velocity; D005260:Female; D006085:Graft Survival; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010180:Pancreatectomy; D051381:Rats; D011920:Rats, Inbred WF; D014182:Transplantation, Autologous
D007328:Insulin