Correlation between insulin requirements and anti-galactose antibodies in patients with type 1 diabetes transplanted with neonatal pig islets

Abstract

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.

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

“…Pancreatic islets were inserted together with neonatal porcine SeC in a porous chamber and placed subcutaneously in the anterior abdominal wall of young diabetic patients, without immunosuppressive treatment. The patients did not show any complications in a 7-years follow-up, and a half of the grafted patients significantly diminished their insulin doses [86,87]. Finally, SeC have been employed in different experimental models of diseases to take advantage of their release of trophic and anti-inflammatory factors (Table 2).…”

Do porcine Sertoli cells represent an opportunity for Duchenne muscular dystrophy?

“…On the side of the biomaterial used, (a) highly biocompatible, clinical grade alginate (endotoxin content less than 0.5 EU/mL, as required for human transplants) was used for the production of microcapsules; (b) alginate‐based microcapsules have shown long‐term survival and activity of entrapped cells with porcine IGF‐1 being detected in the serum of mice treated with porcine‐derived SeC up to 1 year after injection; and (c) alginate‐based microcapsules containing human pancreatic islets have been employed in a phase I clinical trial in which they were transplanted ip in non‐immunosuppressed type 1 diabetic patients with no undesired effects reported . On the side of SeC, (a) SeC were purified from testis of SPF (specific pathogen free) piglets, that is, animals suitable for engraftment in humans; (b) MC‐SeC were injected ip in spontaneous type 2 diabetes non‐human primates (rhesus macaques) resulting in reduction of plasma glucose and B lymphocytes, and absence of adverse effects; (c) neonatal porcine SeC were inserted together with pancreatic islets subcutaneously in a porous chamber in the abdominal wall of young diabetic patients, in the absence of immunosuppressive treatment, and half patients significantly diminished their insulin doses with no complications reported in a 7‐year follow‐up …”

“…No need for immunosuppression - porcine SeC were inserted together with pancreatic islets subcutaneously in a porous chamber in the abdominal wall of young diabetic patients, in the absence of immunosuppressive treatment, and half patients significantly diminished their insulin doses with no complications reported in a 7-year follow-up. 106,107 The use of pig cells, tissues and organs meets the general need to satisfy the increasing request for transplantation by humans and neither antibodies against PERV nor provirus integration in patients' blood cells was observed. 111 The reason why PERVs are not transmitted is that they probably are not released from the transplants or they are neutralized by the host cellular defence and immune system.…”

Xenotransplantation literature update, May–June 2011

“…Esquivel‐Pérez et al. [5] analyzed the levels of anti‐galactose‐α1,3‐galactose (Gal) and general anti‐pig antibodies in 21 type 1 patients with diabetes at 2.6 to 7.7 yrs post‐transplantation of porcine islets together with Sertoli cells inside a device without immunosuppression. This highly controversial trial was previously criticized by the International Xenotransplantation Association because of ethical concerns and by the lack of encouraging data on, e.g., insulin staining, pig C‐peptide measurements, and HbA1C levels [6,7].…”