Islet isolation and autotransplantation in pigs.

ABSTRACT

Despite recent considerable progress in the isolation and purification of porcine pancreatic islets the final proof of functional integrity has not yet been performed. In the present study the feasibility, technical problems and posttransplant metabolic function of islet transplantation in the pig were investigated. Intraductal collagenase perfusion technique for islet preparation was used in 27 landrace pigs and eight minipigs followed by intraportal or intrasplenic transplantation of the islets. Islet purification was performed by dextran gradient in six preparations. Islet quantification, portal vein pressure measurements, intra- and postoperative complications and postoperative graft function were monitored. Between 1.73 x 10(5) and 11.4 x 10(5) islet containing fragments (8.23 x 10(3)-54.28 x 10(3) islet containing fragments/kg recipient body weight) were transplanted. Portal vein thrombosis occurred in 4 animals with significantly elevated portal pressure (p = 0.0001). 11 of 27 landrace pigs died due to postoperative complications. None of the minipigs was lost due to perioperative mortality (p = 0.031). Four of eight landrace pigs with intrasplenic grafts (50%) were normoglycemic and two of eight landrace pigs with intrahepatic transplants (25%) were normoglycemic. In minipigs two out of four (50%) with intrasplenic transplants and two of four (50%) with intraportal transplants were normoglycemic. The results in glucose metabolism as measured with intravenous glucose tolerance tests and calculated by K-values were statistically significantly different between normoglycemic and hyperglycemic animals (landrace pigs p = 0.0002 and minipigs p = 0.0005). Longevity was prolonged in normoglycemic animals as compared to hyperglycemic and apancreatic animals. It is concluded that successful islet isolation and transplantation is feasible in the landrace pig and the minipig while the landrace pig appears to be more susceptable to perioperative mortality.