Human Fetal Islet Transplantation in Type 1 Diabetics: Comparison of Immunological Effects Between Multiple Implantation Regimens

Abstract

Previous studies have suggested that the multiple transplants might be equally metabolically efficient to a single regimen for human adult islets. The aim of this study was to compare immunological and metabolic parameters after each of the two regimens of human fetal islets (HFI). Group A single transplants (n = 9) had 180 ± 20 × 1000 HFI equivalents (IEQs) implanted via a single intramuscular injection. In group B multiple transplants (n = 8) islets were implanted by three consecutive injections of 60 ± 10 × 1000 IEQs at 7-day intervals. We analyzed the immunological parameters of CD 4/CD 8 T lymphocyte ratios; islet cell antibodies (ICAs) and insulin antibodies (IAs). We estimated insulin secreting capacity (ISC) as the metabolic parameter. We observed that the CD 4 +/CD 8 + T-cell ratio increased, peaking on day 90, in similar fashion in both groups: day −1: A = 1.18 ± 0.03 versus B = 1.19 ± 0.04; on day 90: A = 1.79 ± 0.09, versus B = 1.75 ± 0.08 ( P = NS) immediately before the decrease in C-peptide levels. Thereafter the ratios rapidly decreased without statistical differences. The levels of ICAs did not change. The levels of IAs, which were increased before transplant, then decreased without statistical differences between the groups. The values of ISC increased after transplant and then decreased similar to the T-cell ratio. Our results demonstrated that regimens of multiple and single HFIs did not show differences in the kinetics of the immunological response presumably mediating graft destruction. The CD 4/CD 8 ratio increased as the C-peptide level decreased, peaking on day 90 at the time of a decrease in C-peptide. These results may be useful for clinical studies of HFIs for type 1 diabetic patients.