SummaryPancreas transplantation is an option to achieve better metabolic control and decrease chronic complications in patients with diabetes. Xenotransplantation becomes an important alternative. In this study, we show the clinical outcome of patients with type 1 diabetes transplanted with neonatal pig islets without immunosuppression. In a longitudinal study of 23 patients with type 1 diabetes, who received porcine islets between 2000 and 2004, we registered demographic and clinical characteristics every 3 months and chronic complications evaluation yearly. Porcine C-peptide was measured in urine samples under basal conditions and after stimulation with l-arginine. More than 50% were female, median current age was 20·8 years, median diabetes duration at transplantation 5·5 years, median current diabetes duration 11 years and median time post-transplantation 5·7 years. Their media of glycosylated haemoglobin reduced significantly after the first transplantation. Insulin doses remain with a reduction greater than 33% in more than 50% of the patients. Before transplantation, 14 of the 21 patients presented mild chronic complications and currently only two patients presented these complications. Porcine C-peptide was present in all urine samples under basal conditions and increased post-stimulation with l-arginine. These patients achieved an excellent metabolic control after the first transplantation. This could explain, as well as the remaining function of transplanted cells, the low frequency of chronic complications compared to patients with similar diabetes duration and age.
In order to alleviate the shortage of human donors, the use of porcine islets of Langerhans for xenotransplantation in diabetic patients has been proposed as a solution. To overcome rejection, we have developed a procedure for protecting the islets by combining them with Sertoli cells and placing them in a novel subcutaneous device, that generates an autologous collagen covering. A type 1 diabetic woman was closely monitored for 10 months, and then transplanted in two devices with two months of difference and a third time after 22 months. Here we present a three-yr follow-up. The close monitoring induced a rapid decrease in exogenous insulin requirements, which stabilized between 19 and 28 IU/d for nine months. After transplantation, the requirements reduced further to below 6 IU/d and for some weeks she was insulin free. Glycosylated hemoglobin levels decreased concomitantly. Porcine insulin could be detected in the serum after a glucose challenge and insulin positive cells inside a removed device after two yr. No complications have arisen and no porcine endogenous retrovirus infection has been detected through PCR and RT-PCR. This case demonstrates the feasibility of using the xenotransplantation of porcine cells to alleviate metabolic complications and insulin requirements in type 1 diabetic patients.
The technique allowed us to obtain NPCC with optimal viability, functionality, purity, and endurance for use in research.
We describe an alternative strategy for preparing and identifying cultured SC for further assays of metabolic activity or in transplantation models. Establishing a one-step Liberase-digestion method for isolation, evaluating viability and apoptosis by more sensitive methods, and detecting specific markers in culture can help to evaluate the quality of cultured cells. Specific cell markers for identifying SC may be critical when identifying SC outside the testis, in contrast with vimentin which is useful only for in situ cells.
SummaryPig xenografts represent an alternative source of organs for transplantation. Immunosuppression can prevent rejection, but involves high risk and cost. New anti-rejection techniques have been developed; however, results have not been successful. Few studies have reported xenoantibody levels in xenotransplanted patients with diabetes and no patients have reported a clinical correlation. We analysed anti-galactose (Gal) and other anti-pig antibody (APA) levels in xenotransplanted patients with type 1 diabetes and the relation to the clinical outcome. Twenty-three patients with type 1 diabetes were transplanted with porcine islets inside a device without immunosuppression. Demographic characteristics, insulin dose and xenoantibody levels at different periods were recorded. Anti-Gal and anti-pig antibodies were measured through indirect enzyme-linked immunosorbent assay (ELISA) and haemolytic anti-pig antibody assay. More than 50% were female; the mean current age, current diabetes duration, diabetes duration at xenotransplantation and time post-transplantation were: 20·8, 11, 5·5 and 5·7 years, respectively. Insulin doses remained with a mean reduction greater than 33% in more than 50% of the patients. The lowest anti-Gal antibody levels were related to the highest insulin dose reductions. This relationship could be explained by the device, Sertoli cells and accommodation process.
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