CLINICAL ISLET TRANSPLANTATION

K.K. Papas¹, M. Bellin¹, D.E. Sutherland¹, K. Mueller², E.S. Avgoustiniatos¹, A.N. Balamurugan³, P.R. Rozak¹, G. Loganathan¹, D. Qian⁴, J.C. Niland⁴, B.J. Hering^1
1Surgery, University of Minnesota, Minneapolis/UNITED STATES OF AMERICA, ²Department Of Surgery, University of Minnesota, Minneapolis/UNITED STATES OF AMERICA, ³Surgery, Schulze Diabetes Institute, Minneapolis/MN/UNITED STATES OF AMERICA, ⁴Information Science, City of Hope, Duarte/CA/UNITED STATES OF AMERICA

Body: Introduction: Meaningful assays that characterize islet potency prior to clinical transplantation are needed. Assays evaluating mitochondrial function, especially cellular oxygenconsumption rate (OCR), have emerged as promising. Correlations with clinical outcomes are, however, lacking. Intraportal islet autotransplant (IAT) in patients with chronic pancreatitis undergoingtotal pancreatectomy offers an attractive setting for evaluating the relationship between islet potency assays and clinical outcomes in the absence of confounding factors, such as auto- andallo-immunity or immunosuppressive drug toxicity.

Methods: Islet membrane integrity (FDA/PI), the ratio of OCR to DNA, and the viable islet dose based on OCR were measured in islet autograft products with purities ranging from 10% to 95% (n=32).Recipients with >6 months of follow up were included in the analysis. IAT recipients with fasting blood sugar <126 mg/dL, 2-hour postprandial blood sugar <180 mg/dL, and HbA1c ≤6.5%without administration of exogenous insulin were deemed insulin independent.

Results: Islet autograft product characteristics are summarized in Table 1. Preparations that resulted in insulin independence had a significantly higher OCR dose (P=0.0014) and purity(P=0.0053).

OCR dose correlated with IAT outcome and predicted insulin independence with high sensitivity and specificity (92% and 100%, respectively), as shown in Figure 1. Values for OCR/DNA and FDA/PI did notcorrelate with insulin independence, and neither did purity, despite the statistically significant difference between the 2 groups. The combination of OCR dose and OCR/DNA needed to predict outcomewhen human, porcine, or rat islets are transplanted under the kidney capsule of diabetic mice was not necessary. This may be related to the difference in the transplantation site and size (kidneycapsule versus liver), but also to the use of autologous as opposed to allo- or xenogeneic tissue.



Conclusion: The preliminary data presented suggest that OCR measurements may be useful for the prospective evaluation of the quality of islet preparations prior to clinical transplantation.

Disclosure: All authors have declared no conflicts of interest.