Transplantation of Cultured Islets from Two-Layer Preserved Pancreases in Type 1 Diabetes with Anti-CD3 Antibody

摘要: We sought to determine whether or not optimizing pancreas preservation, islet processing, and induction immunosuppression would facilitate sustained diabetes reversal after single-donor transplants. Islets were isolated from two-layer preserved pancreata, purified, cultured for 2 days; transplanted into six C-peptide-negative, nonuremic, type 1 diabetic patients with hypoglycemia unawareness. Induction immunosuppression, which began days pretransplant, included the Fc receptor nonbinding humanized anti-CD3 monoclonal antibody hOKT3gamma1 (Ala-Ala) sirolimus. Immunosuppression was maintained sirolimus reduced-dose tacrolimus. Of our recipients, four achieved insulin independence normal HbA1c levels freedom hypoglycemia; one had partial graft function; lost function weeks post-transplant. The insulin-independent showed prolonged CD4+ T-cell lymphocytopenia; inverted CD4:CD8 ratios; increases in percentage of CD4+CD25+ T cells. These cells suppressed in-vitro proliferative response donor and, a lesser extent, third-party Severe adverse events limited transient rash recipient temporary neutropenia three. Our preliminary results thus suggest that combination maximized viable yield, pretransplant culture, preemptive can result successful