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 x 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 x 1000 IEQs at 7-day intervals. We analyzed the immunological parameters of CD4/CD8 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 CD4+/CD8+ 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 CD4/CD8 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.
Subject(s)
Diabetes Mellitus, Type 1/surgery , Fetal Tissue Transplantation/immunology , Fetal Tissue Transplantation/methods , Insulin/metabolism , Islets of Langerhans Transplantation/immunology , Islets of Langerhans Transplantation/methods , CD4-CD8 Ratio , Cell Culture Techniques , Gestational Age , Glucagon , Graft Rejection/prevention & control , Humans , Injections, Intramuscular , Insulin Secretion , Islets of Langerhans/cytology , Islets of Langerhans/embryology , Islets of Langerhans/immunology , Lymphocyte Subsets/immunologyABSTRACT
Previous studies suggest that multiple transplantations might be equally efficient to a single regimen for human adult islets. The aim of this study was to compare metabolic parameters after each of the two regimens of human fetal islet (HFI) transplantation in type 1 diabetics. In group A (single transplant, n = 9), 180 +/- 20 x 1000 HFI equivalents (IEQs) were implanted by a single IM injection; in group B (multiple transplants, n = 8) islets were implanted as three consecutive injections (60 +/- 10 x 1000 IEQs) at 7-day intervals. We analyzed the metabolic parameters on days -1, 30, 60, 90, 120, 150, and 180 after the procedure. Among the metabolic parameters, we evaluated insulin secretion capacity-ISC (C peptide, RIA), metabolic control (HbA1c, chromatography), and insulin daily dose IDD. We found that C peptide levels increased, peaking on day 90 (A: 0.38 +/- 0.15; B: 0.34 +/- 0.19 nmol/L, P = NS) and then rapidly decreasing without differences, the HbA1c levels and IDD decreased in the same manner without differences between the groups. Our results demonstrate that multiple and single islet transplant regimens are equally efficient to temporarily restore a significant ISC with improvement of metabolic and clinical parameters. The results imply that the two regimens have an equal clinical value.