Alejandro, R

Carroll, P

Demetris, AJ

Ricordi, C

Rilo, HLR

Sever, CE

Starzl, TE

Tzakis, A

Zeng, Y

Transplantation Proceedings

English

PubMed

RICORDI, C

SEVER, C. E

CARROLL, P

TZAKIS, A

ZENG, Y

RILO, H. L. R

DEMETRIS, A. J

ALEJANDRO, R

STARZL, T. E

University of Miami: Scholarship Miami

Histologic finding of pancreatic islet tissue following intraportal human islet allotransplantation

D-Scholarship@Pitt

., I . , /3'37 Histologic Finding of Pancreatic Islet Tissue Following Intraportal Human Islet Allotransplantation C. Ricordi. C.E. Sever. P. Carroll. A. Tzakis. Y. Zeng, H.L.R. Rilo, A.J. Demetris, R. Alejandro, and T.E. Starzt THE ultimate test of viability of separated human islets is functional activity after transplantation into a dia-betic recipient. Morphologic identification of insulin-con-taining transplanted islets could provide important correl-ative data and eventually confirm the functional results. The present report describes identification of intrahepatic islet tissue following human islet allotransplantation. MATERIALS AND METHODS Human islets were obtained and transplanted into the liver via portal vein injection following upper-abdominal exenteratton and liver replacement. 1 or following liver or kidney transplantation In type 1 diabetic patients. Liver ttssue was examined from needle biopsy (n = I I. wedge biopsy tn = 2). or at autopsy tn = 2). Immunohistochemical stains were performed on formalin-fixed. paraffin-embedded tissue using the avidin-biotin complex meth-od.z A panel of antibodies directed against insulin. glucagon. mononuclear cells. and class 11 antigens was used. RESULTS AND DISCUSSION In all patients. islet tissue was mostly found i.n subcapsular location. In patients whd underwent upper-abdominal ex-enteration and liver-islet replacement. islets were found in several sections from two patients ( 17 and 109 days after transplantation). No significant surrounding inflammatory reaction was demonstrated. The insulin and glucagon stains unequivocally demonstrated beta and alpha granu-lation in the majority of the islet cells. In type I diabetic patients who received a combined liver-islet (n = I. biopsy on postoperative day 15) or kidney-islet tn = 2. days 2 and 5 posttransplant) allograft. the islet tissue was often asso-ciated with a mild. predominantly lymphocytic infiltrate. In one patient who received a liver-islet transplant. the needle biopsy obtained 15 days after transplantation re-vealed a mixed portal infiltrate surrounding an islet. which reflected hypoperfusion injury of the liver allograft. In a patient who died 5 days following combined kidney-islet transplantation from aspiration pneumonia. intrahepatic islet tissue was often associated with a dense mixed infiltrate of lymphocytes and macrophages. Most of the lymphocytes stained positive with T-cell markers. and several of them were also positive for HLA-DR. suggest-976 ing T-cell activation. HLA-DR stain was also strongly positive in histiocytic cells with dendritic morphology, possibly representing antigen-presenting cells. Interest-ingly, the islet cells remained HLA-DR negative. despite the surrounding inflammatory reaction. A wedge liver biopsy that was taken from a type I diabetic patient who required reexploration for evacuation of a perinephric hematoma 2 days after combined kidney-islet transplantation revealed a mild reactive mononuclear infiltrate around the intrahepatic islet tissue. In summary. mononuclear cell infiltrate charactenzed intrahepatic islets following allotransplantation in type I diabetic patients. In contrast. in patients receiving a com-bined liver-islet allograft following upper-abdominal exen-teration. no significant inflammatory response was ob-served. The mononuclear cell infiltrate observed in type I dia-betic patients indicates that a specific inflammatory reac-tion and/or rejection is most likely to occur in these patients. Alternatively. the different finding could reflect a difference in the time of evaluation. In fact. Ii ver tissue was analyzed earlier in type I diabetic patients who received a combined kidney-islet allograft (2 and 5 days posttrans-plant) compared to patients undergoing upper-abdominal exenteration and liver-islet replacement t 17 and 109 days posttransplant) . REFERENCES I. Tzakis A. Ricordi C. Alejandro R. et al: Lancet 336:402. 1990 2. Hsu SM. Raine L. Fanger H: J Histochem Cytochem 29:Sn. 1981 From the Transplant Institute. University of Pittsburgh School of Medicine. Pittsburgh. Pennsylvania, and the Diabetes Research InstitUte. University of Miami School of Medicine, Miami. Florida. Supported In pan by Juvenile Diabetes Foundation Research Grant no. 1911421. Address reprint requests to Dr Camillo Ricordi. The Transplant institute. University of Pittsburgh. 5C Falk Clinic. 3601 Fifth Ave-nue. Pittsburgh. PA 15213. © 1992 by Appleton & Lange 0041·1345192JS3.001 +0 Transplanlation ProceediItgS. Vol 24. No 3 (June). 1992: p 976 

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Histologic finding of pancreatic islet tissue following intraportal human islet allotransplantation

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