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

Abstract

PURPOSE: To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. METHODS: Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. RESULTS: The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. CONCLUSIONS: In the animals with immunosupression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

Is there a relationship between lipids metabolism and splenic surgeries?

“…The respect due to this organ because of its importance in the physiopathology of many diseases has favored the development of multiple operations aiming at the preservation of the spleen, with a consequent reduction of sepsis rates and of postoperative hematologic disorders 19 . Total splenectomy, which used to be extensively indicated in the past, is being progressively replaced with spleen-conserving procedures such as spleen suture, partial splenectomy, subtotal splenectomy or autogenous spleen tissue implant after spleen removal 18,20,21 .…”

Pancreatic Islet Transplantation: From Dogs to Humans and Back Again

“…Whereas canine diabetes mellitus has been described as an ideal preclinical model for T1DM in people, most islet transplant studies were actually carried out in healthy research animals that underwent pancreatectomy or chemically induced diabetes, where success would be expected to be higher than in clinical patients with autoimmune induced beta cell destruction. Nonetheless, a vast amount of information has been assembled in over 40 studies involving canine islet isolation, preservation, or transplantation (Table ) . A small number of recent studies have even shown some promise in resolution of spontaneous diabetes in client‐owned dogs (Table ) …”