Current Status of Clinical Islet Transplantation

Abstract

The realization that conventional treatment of insulin dependent diabetes mellitus (IDDM) with diet and insulin injections is apparently insufficient to prevent and even stabilize the secondary complications of diabetes generated interest in endocrine pancreas replacement therapy with the hope that normoglycemia achieved by the replacement of normal functioning islets may prevent, stop or even reverse late diabetic complications.Endocrine pancreas replacement has been attempted by either transplantation of vascularized pancreatic grafts or by transplantation of isolated islets of Langerhans as free grafts. Present situation in pancreas organ transplantationAlthough the clinical experience with islet transplantation is emphasized in this report, a brief overview on what can be achieved by pancreas transplantation will be given in advance. During the last years there has been substantial progress in the field of vascularized pancreatic transplantation, and the results now begin to approach those obtained with other vascularized organ grafts {Sutherland ). In an analysis of 1001 pancreas transplants reported to the International Pancreas Transplant Registry since 1966, 1-year actuarial graft function (insulin independent) and recipient survival rates were 35% and 75% respectively and in an analysis of the periods from 1966 to 1977 (n=64), 1978 to 1982 (n=201), 1983 to 1984 (n=298), and 1985 to 1986 (n=438), 1-year actuarial graft function rates were 3%, 21%, 39%, and 44%. Of the 329 grafts that were functioning at the time of analysis, 169 were less than 1 year posttransplant, whereas 160 were more than 1 year posttransplant, including 16 that were more than 4 years, the longest being 8.2 years (Sutherland and Moudry 1987b).With regard to the disappointing 4-year pancreas function rate the question arises as to whether the inevitable risk of vascularized pancreas transplantation can be justified. Beneficial influence on complications such as retinopathy, neuropathy, and peripheral vascular disease in patients with a successful pancreas transplant has not been convincingly demonstrated (Gray and Morris 1987). A recent study of the Minnesota group (Ramsay et al. 1988) provides evidence that pancreas transplantation and subsequent normoglycemia over 24 months in patients with type 1 diabetes of long duration (mean, 21 years) neither reverses nor prevents the progression of diabetic retinopathy. Solders et al. (1987) have presented data indicating that diabetic neuropathy is not reversed by successful pancreas and renal transplantation.Furthermore, it has not yet been proven that patient survival rate and quality of life are significantly better after simultaneous pancreas and kidney transplantation in recipients with end-stage diabetic nephropathy (ESDN) than in those ESDN-patients with kidney grafts alone. Interest in application of pancreas transplantation to nonuremic, non-kidney-transplant recipients is increasing, because preliminary evidence (Ramsay et al. 1988) suggests that a salubrious effect on late compli...

Transplantation of Purified Islet Cells in Diabetic Rats: II. Immunogenicity of Allografted Islet β-Cells

“…Diabetes 40:920- 30,1991 T ransplantation of pancreatic islets in humans faces more technical problems than that of a vascularized pancreas (1,2). However, the ability of pretreating isolated islet tissue before its implantation creates several advantages over classical organ grafting.…”

The bladder drainage technique in pancreas transplantation ? the T�bingen experience

“…Long-term complete euglycaemia can only be achieved at present by transplantation of insulin producing tissue. Since in the human setting islet transplantation is still in an experimental stage (Hering et al 1988) pancreatic transplantation remains as the only treatment modality to cure diabetes. Until recently, however, the results of pancreatic transplantation were clearly inferior to those of other solid organ transplantations (Sutherland et al 1991).…”

Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islet allografts

“…However, after 20 years of intensive research, islet transplantation is still not readily available for Type 1 (insulin-dependent) diabetic patients. The main causes are 1) that islet isolation techniques are inappropriate for obtaining large amounts of islet tissue, and 2) a lack of appropriate means to prevent graft rejection after transplantation [1][2][3].…”