Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody

Am J Transplant. 2004 Mar;4(3):390-401. doi: 10.1046/j.1600-6143.2003.00351.x.


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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • CD3 Complex / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / surgery*
  • Female
  • Humans
  • Islets of Langerhans / physiology
  • Islets of Langerhans Transplantation / immunology*
  • Male
  • Middle Aged
  • Muromonab-CD3 / immunology*
  • Pancreas / cytology
  • Pancreas / immunology
  • Pancreas / surgery
  • T-Lymphocyte Subsets / immunology
  • Tissue Donors


  • CD3 Complex
  • Muromonab-CD3