IMMUNOCYTOCHEMICAL DETECTION AND CHARACTERIZATION OF INTRAHEPATIC HUMAN PANCREATIC-ISLETS AFTER COMBINED LIVER-ISLET ALLOTRANSPLANTATION

The unique availability of an explanted liver-islet allograft, removed for primary nonfunction of the liver, led us to evaluate distribution and phenotype of exocrine and endocrine components of the pancreatic graft. Immunocytochemistry was used to map patterns of gene products f or islet hormones, proprotein processing enzymes, pan-neuroendocrine m arkers, and pancreatic exocrine markers. When compared with age-matche d control pancreases, insulin-, glucagon-, somatostatin-, and pancreat ic polypeptide-producing cells were similarly represented and distribu ted within the grafted islet. We also demonstrate that the intrahepati c transplanted islets retained the enzyme machinery able to process th e hormone precursors into bioactive fragments. In the clinical setting , this resulted in an immediate functioning of the graft and insulin-i ndependence of the patient one month after transplantation. The purity in islets, as assessed by immunocytochemistry with antibodies to tiss ue constituents of endocrine and exocrine lineages, was around 40%. De spite the massive intraportal presence of pancreatic acinar tissue, no signs or symptoms attributable to ectopic hypersecretion of exocrine enzymes occurred. In fact, when tested with antibodies to such enzymes , low levels of immunoreactivity were observed in the grafted acinar c ells.