Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets

Abstract

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.

Sustained Expression of Insulin by a Genetically Engineered Sertoli Cell Line after Allotransplantation in Diabetic BALB/c Mice1

“…Besides nurturing these autoimmunogenic germ cells, SCs also protect them from an immunologic response by expressing and secreting several immunoregulatory factors, thus contributing to testis' immune privilege. Immune modulation by SCs is not restricted to the testis as SCs also survive when transplanted to ectopic sites (outside the testis), across immunological barriers (i.e., allo-or xenotransplantation), without the need for immunosuppressive drugs [5][6][7][8][9][10][11][12][13]. This suggests that immune-privileged SCs used as a vehicle for cell-based gene therapy have the potential to overcome the obstacle of immune rejection.…”

Survival of encapsulated islets: More than a membrane story

“…Sertoli cells were also able to enhance survival of islets graft in xenogeneic recipients [171173] . Finally, coencapsulated porcine islets and Sertoli cells were implanted into human subjects in a controversial Mexican clinical trial [8,174,175] . Some of the transplanted patients experienced reduction in their requirements for insulin therapy for up to 3 years.…”

Regenerative Medicine and Tissue Engineering for the Treatment of Diabetes

“…Interestingly all patients improved glycemic control after transplantation irrespective of the amount of insulin reduction. Long-term follow-up of those patients revealed that all patients have positive porcine C-peptides in urine (Valdes-Gonzalez et al, 2010). In terms of safety, routine microbiological screening of all patients and close family have been consistently negative, although two patients exhibited transient chimerism as evidenced by porcine DNA thru polymerase chain reaction (PCR).…”

“…Especially, creating a new viral disease by xeno-transplantation must be avoided. Infection of porcine endogenous retrovirus after xeno-transplantation into immune compromised mice demonstrated the risk of the combination of immunosuppression and xenotransplantation (van der Laan LJ et al, 2000). Therefore current bio-artificial islet transplantations have been performed without immunosuppression.…”