ABSTRACT
BACKGROUND: The long-term viability and function of transplanted encapsulated neonatal porcine islets was examined in a diabetic patient. METHODS AND RESULTS: A 41-yr-old Caucasian male with type 1 diabetes for 18 yr was given an intraperitoneal transplant of alginate-encapsulated porcine islets at the dose of 15,000 islet equivalents (IEQs)/kg bodyweight (total dose 1,305,000 IEQs) via laparoscopy. By 12 weeks following the transplant, his insulin dose was significantly reduced by 30% (P = 0.0001 by multiple regression tests) from 53 units daily prior to transplant. The insulin dose returned to the pre-transplant level at week 49. Improvement in glycaemic control continued as reflected by total glycated haemoglobin of 7.8% at 14 months from a pre-transplant level of 9.3%. Urinary porcine C-peptide peaked at 4 months (9.5 ng/ml) and remained detectable for 11 months (0.6 ng/ml). The patient was followed as part of a long-term microbiologic monitoring programme which subsequently showed no evidence of porcine viral or retroviral infection. At laparoscopy 9.5 yr after transplantation, abundant nodules were seen throughout the peritoneum. Biopsies of the nodules showed opacified capsules containing cell clusters that stained as live cells under fluorescence microscopy. Immunohistology noted sparse insulin and moderate glucagon staining cells. The retrieved capsules produced a small amount of insulin when placed in high glucose concentrations in vitro. An oral glucose tolerance test induced a small rise in serum of immuno-reactive insulin, identified as porcine by reversed phase high pressure liquid chromatography. CONCLUSION: This form of xenotransplantation treatment has the potential for sustained benefit in human type 1 diabetics.
Subject(s)
Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation/methods , Transplantation, Heterologous/methods , Adult , Animals , C-Peptide/urine , Cell Survival , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/metabolism , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Male , Pregnancy , Swine , Time Factors , Treatment OutcomeABSTRACT
Shortage of human donor organs for transplantation has prompted evaluation of animals as an alternative donor source. Pigs are the most acceptable candidate animals but issues of xenozoonozes remain. Despite careful monitoring of high-health-status (HHS) pigs, there is still a risk that their tissues may carry infectious agents. Furthermore, pathogens which are significant in xenotransplantation are not necessarily those of veterinary importance. The detection of these potentially transmissible infectious agents may require the development and application of new surveillance technologies. We present data on monitoring for five potentially xenotic viruses in New Zealand pig herds, namely pig cytomegalovirus (PCMV), pig lymphotropic herpesvirus (PLHV), encephalomyocarditis virus (EMCV), pigcircovirus (PCV), and hepatitis E virus (HEV). These five viruses are either potentially oncogenic, establish persistent infection, or are known to be zoonotic. This study has expanded significantly the information on porcine viruses in New Zealand. Using this information, it is now possible to complete protocols for monitoring pig herds and tissues prior to their use in xenotransplantation. The study resulted in selection of a possible source herd for swine-to-human islet transplantation.
