In vivo quality control of human islets in the immunodeficient mouse to predict islet function in man: A retrospective study in 87 clinical transplants

Abstract Objective. This retrospective study in 87 clinical islet transplants sought to determine if the quantitative in vivo islet potency assay (QIVIPA) based on human c-peptide measurement in normoglycemic immunodeficient mice transplanted with 1% of clinical islet transplant (n = 165) could predict islet function in man after transplantation (tx). Since each recipient receives a mean of 2.7 grafts in our center, the ultimate goal of this work was to prospectively determine the functional islet mass required in 1–3 transplants in the QIVIPA mice to achieve optimal long-term islet function (beta score ≥ 7) in man. Methods. Islet preparations that met in vitro release criteria (200,000 IEQ, viability ≥ 80%, sterility) were transplanted in severe type 1 diabetic patients (n = 87). 2% of the preparation was used for in vitro quality controls, and 2% for in vivo controls: tx under the kidney capsule of two normoglycemic nude or RAG2 mice where fasting c-peptide and glycemia were measured over 30 days. Human islet function was defined by immediate graft function (hCP increase 7 days after tx), primary graft function (PGF = beta score 1 month after the last tx) and beta score at 1 year. Results. The QIVIPA model is robust and reproducible with two mice transplanted per human islet preparation (P  Conclusion. Evidence from this retrospective study on 87 clinical islet transplants in 165 mice suggests that in vivo quantitative islet potency assays like QIVIPA in normoglycemic immunodeficient are a key indicator of the quality of manufactured clinical graft preparations as they predict islet function in man, both early function at 7 days post tx, PGF (beta score 1 month after the last tx), and 1-year beta score even when multiple grafts are transplanted per recipient.