Pancreatic islet cell autotransplantation in the canine model

Pancreatic islet allograft in spleen with immunossuppression with cyclosporine. Experimental model in dogs

“…The mechanical manipulation represented by the centrifuge and the transfer using pipettes, as well as the exposure to hyperosmolar chemical substances during the purification process of islets, can damage and fragment the islets, altering their viability and functionality at the site of ectopic transplantation 2,5,[13][14][15] . These events may have contributed to the failure of the grafts in the animals that were subjected to auto-and allotransplantation.…”

“…All of these technical peculiarities of preparation and implementation of pancreatic islet transplantation imply the need for a greater initial volume of islets to compensate for the loss of viable islets during the many stages of the process [5][6][7] . The inadequate mass of beta cells is considered the most frequent non-immunological cause for the failure of allogenic transplant of pancreatic islets 5,13,14 .…”

“…The inadequate mass of beta cells is considered the most frequent non-immunological cause for the failure of allogenic transplant of pancreatic islets 5,13,14 . Because the preparation of "purified" canine islets is estimated to yield approximately 20% of the total initial content of the intact pancreas 3,5,15 , it is expected that the secretion of insulin should be significantly lower in the animals subjected to pancreatic transplantation than in the control animals 4,5 . In this study, it was found that there was a significant reduction in the insulin levels between pre-and post-transplant in the animals of groups C, D, and E. This reduction was attributed to the reduction of the functionally active endocrine tissue mass transplanted into the spleen because of the process of pancreatic islet preparation.…”

“…Pancreatic islet transplantation has been intensively studied as an alternative to vascularized transplant of the pancreas 3,4 . The disadvantages of pancreatic islet transplant are the difficulty of isolating viable and functioning human islets in sufficient quantities to maintain a normoglycemic state, and the immunogenocide of the islets that requires considerable amounts of immunosuppressive drugs to prevent rejection 5 . However, the more compact pancreas of large mammals yields a low number of functionally viable and isolated pancreatic islets caused by the strong connections between their own islets and the pancreatic exocrine tissue that surrounds them [6][7][8][9] .…”

“…Third, the response to food intake should be studied, because it is an accurate indicator of the metabolic control achieved with the insulin supplementation caused by to the pancreatic islet transplantation 1 . Therefore, the search for experimental models of isolation and transplantation involving efficiency and simplification of the procedures remains an objective to be pursued so that the clinical transplant of pancreatic islets can become a safe and efficient therapeutic option 5 . The purpose of this study was to evaluate the functional behavior of the allograft with immunosuppression with cyclosporine of pancreatic islets isolated using the method of mechanical-enzymatic preparation (stationary collagenase digestion and with dextran discontinuous density gradient) in the spleen of dogs.…”