Enhanced Prediction of Porcine Islet Yield and Posttransplant Outcome Using a Combination of Quantitative Histomorphometric Parameters and Flow Cytometry
Abstract:Prediction of islet yield and posttransplant outcome is essential for clinical porcine islet xenotransplantation. Although several histomorphometric parameters of biopsied porcine pancreases are predictive of islet yield, their role in the prediction of in vivo islet potency is unknown. We investigated which histomorphometrical parameter best predicts islet yield and function, and determined whether it enhanced the predictive value of in vitro islet function tests for the prediction of posttransplant outcome. We analyzed the histomorphometry of pancreases from which 60 adult pig islet isolations were obtained. Islet function was assessed using the -cell viability index based on flow cytometry analysis, oxygen consumption rate, ADP/ATP ratio, and/or concurrent transplantation into NOD/SCID mice. Receiver operating characteristic (ROC) analysis revealed that only islet equivalent (IEQ)/cm2 and the number of islets >200 m in diameter significantly predicted an islet yield of >2000 IEQ/g (p < 0.001 for both) and in vivo islet potency (p = 0.024 and p = 0.019, respectively). Although not predictive of islet yield, a high proportion of large islets (>100 m in diameter) best predicted diabetes reversal (p = 0.001). Multiple regression analysis revealed that the -cell viability index (p = 0.003) and the proportion of islets >100 m in diameter (p = 0.048) independently predicted mean posttransplant blood glucose level (BGL). When BGL was estimated using both these parameters [area under the ROC curve (AUC), 0.868; 95% confidence interval (CI), 0.730‐1.006], it predicted posttransplant outcome more accurately than the -cell viability index alone (AUC, 0.742; 95% CI, 0.544‐0.939). In conclusion, we identified the best histomorphometric predictors of islet yield and posttransplant outcome. This further enhanced the predictive value of the flow cytometry analysis. These parameters should be useful for predicting islet yield and in vivo potency before clinical adult porcine islet xenotransplantation.
Document Type: Research Article
Affiliations: Xenotransplantation Research Center, Seoul National University Hospital, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
Publication date: 2010-03-01
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