Abstract
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 hOKT3γ 1 (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.
Original language | English (US) |
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Pages (from-to) | 390-401 |
Number of pages | 12 |
Journal | American Journal of Transplantation |
Volume | 4 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2004 |
Keywords
- Autoimmunity
- CD4CD25 T cells
- Diabetes mellitus
- HOKT3γ 1 (Ala-Ala)
- Humanized OKT3
- Hypoglycemia
- Immunosuppression
- Insulin independence
- Islet culture
- Islet transplants
- Perfluorocarbon
- Perfluorodecalin
- Rapamycin
- Single-donor