Clinical Islet Transplantation — Registry Report, Accomplishments in the past and Future Research Needs

Abstract

This review provides the results of a recent analysis of the Islet Transplant Registry on clinical adult islet transplants performed worldwide through June 30, 1992. Between December 12, 1893 and June 30, 1992, 167 adult islet transplants were performed at 25 institutions worldwide, including 104 at 9 institutions in North America, 62 at 15 institutions in Europe, and 1 elsewhere. The total number of diabetic patients reported to be insulin independent after adult islet allotransplantation through June 30, 1992, was 19. In an analysis by era, the percentage of patients that showed positive basal C-peptide levels (i.e., > or = 1 ng/mL at > or = 1 mo) posttransplant, and that became insulin independent (> 1 wk) in the 1985-1989 era (n = 35 cases) were 20% and 6%, and in the 1990-1992 era (n = 69 cases) were 64% and 20%, respectively, and thus have improved significantly (p < 0.001 and p < 0.05). For the 1990-1992 period, the percentage of patients who showed positive basal C-peptide levels post-transplant, and who became insulin independent in the single donor pancreas group (n = 31 cases) were 52% and 13%, and in the multiple donor pancreata group (n = 36 cases) were 75% and 28%, respectively. Islet graft function rates were nearly identical for grafts prepared from pancreata stored < or = 6 h (n = 27) and > 6 < or = 12 h (n = 29), so that 67% and 72% showed positive basal C-peptide levels, and 30% and 21% of the recipients became insulin independent, respectively. No single patient showed islet graft function sufficient to allow withdrawal from insulin, if the pancreata have been stored for more than 12 h. In regard to recipient category for the six groups, namely IAK (islet after kidney), SIK (simultaneous islet kidney transplantation), SIL (simultaneous islet liver transplantation), SIL(C) (simultaneous islet liver transplantation after cluster operation), SIKL (simultaneous islet kidney liver transplantation), and SIH-L (simultaneous islet heart-lung transplantation), the number of patients who showed positive basal C-peptide levels post-transplant was 11 (58%), 17 (57%), 5 (83%), 8 (80%), 1 (50%), and 0 (0%), and the number of insulin independent patients was 4 (21%), 4 (13%), 0 (0%), 6 (60%), 0 (0%), and 0 (0%), respectively. Comparing the two largest recipient categories, namely IAK and SIK, no difference in the outcome of these transplants was apparent.(ABSTRACT TRUNCATED AT 400 WORDS)

Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion

“…[Diabetologia (2002) The insulin-secreting islets comprise only a small fraction of the whole pancreas (~1%); therefore, the transplantation of purified islets rather than the whole pancreas seems to be a reasonable approach to control metabolic dysfunction in patients with Type I (insulindependent) diabetes mellitus. Although the survival of vascularised pancreas allografts at one year has significantly improved following the introduction of T cellspecific immunosuppressants such as cyclosporin and FK506 [1], the survival of pancreatic islet grafts under the same immunosuppressive regimen is still under 30% one year after transplantation [2]. However, a current study reports that seven consecutive patients attained sustained insulin independence after pancreatic islet transplantation [3].…”

“…Although the survival of vascularised pancreas allografts at one year has significantly improved following the introduction of T cellspecific immunosuppressants such as cyclosporin and FK506 [1], the survival of pancreatic islet grafts under the same immunosuppressive regimen is still under 30% one year after transplantation [2]. However, a current study reports that seven consecutive patients attained sustained insulin independence after pancreatic islet transplantation [3].…”

Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipient characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft

“…The majority of these methods made use of cultured islet tissue which ± in rodents ± is known to be less immunogenic than freshly isolated islet preparations [10,11]. So far, studies in man have mainly used freshly isolated tissue, sometimes after a period of cryopreservation [2±7]; their long-term survival in IDDM patients was only observed following induction immunosuppression with anti-T-cell globulins and continuous anti-rejection therapy [1±7]; however, 90 % of implants with this treatment failed [6,8]. We examined whether cultured beta-cell preparations can survive in IDDM patients under maintenance immune suppression for a prior kidney graft without administration of anti-T-cell globulins.…”

Tolerance Induction and Endogenous Regeneration of Pancreatic β-Cells in Established Autoimmune Diabetes

“…Several approaches to replace damaged pancreatic tissue have been attempted, including the transplantation of allogeneic pancreas [57], allogeneic islet grafts [58], and autologous islet transplantation [59]. Another approach involves the production of insulin-producing tissue and cells by in vitro growth of human β-cells from the epithelium of pancreatic ducts or from acinar cells [60,61] or by embryonic or adult stem cells [62,63].…”