Incompatibility between human blood and isolated islets of Langerhans - A finding with implications for clinical intraportal islet transplantation?

The remarkable difference in success rates between clinical pancreas transp lantation and islet transplantation is poorly understood, Despite the same histocompatibility barrier and similar immunosuppressive treatments in both transplantation procedures, human intraportal islet transplantation has a much inferior success rate than does vascularized pancreas transplantation, Thus far, little attention has been directed to the possibility that islet s transplanted into the blood stream may elicit an injurious incompatibilit y reaction, We have tested this hypothesis in vitro with human islets and i n vivo with porcine islets, Human islets mere exposed to nonanticoagulated human ABO-compatible blood in surface-heparinized polyvinyl chloride tubing loops. Heparin and/or the soluble complement receptor 1 (sCR1) TP10 were t ested as additives. Adult porcine islets were transplanted intraportally in to pigs, and the liver was recovered after 60 min for immunohistochemical s taining. Human islets induced a rapid consumption and activation of platele ts. Neutrophils and monocytes were also consumed, and the coagulation and c omplement systems were activated, Upon histological examination, islets wer e found to be embedded in clots and infiltrated with CD11(+) leukocytes, Fu rthermore, the cellular morphology was disrupted. When heparin and sCR1 mer e added to the blood, these events were avoided. Porcine islets retrieved i n liver biopsies after intraportal islet allotransplantation showed a morph ology similar to that of human islets perifused in vitro. Thus, exposure of isolated islets of Langerhans to allogenic blood resulted in significant d amage to the islets, a finding that could explain the unsatisfactory clinic al results obtained with intraportal islet transplantation. Because adminis tration of heparin in combination with a soluble complement receptor abroga ted these events, such treatment would presumably improve the outcome of cl inical islet transplantation by reducing both initial islet loss and subseq uent specific immune responses.