PERSONAL DE APOYO
OTTAVIANO Graciela Mabel
congresos y reuniones científicas
Título:
Pancreatic islets xenotransplantation in dogs with diabetes type 1
Autor/es:
A ABALOVICH; MA MÜLLER; V CASTILLO; A PISAREVSKY; G OTTAVIANO; R GOMEZ FIGUEROA; DR GRANA; J MILEI
Lugar:
Buenos Aires
Reunión:
Congreso; World Congress of Cardiology 2008; 2008
Institución organizadora:
World Heart Federation
Resumen:
Type 1 diabetes mellitus is a Public Health concern given the number of patients affected and the severe complications caused by the disease. Although insulin treatment is useful, long-term complications could not be avoided and labile patients are a concern. Pig islet xenotransplantation represents an attractive way of solving the shortage of human organs for transplantation problem and microencapsulation avoids the need of immunosuppression. The late onset and slow progression of beta cell dysfunction in canine diabetes resembles latent autoimmune diabetes of the adult in man. The objective of this study is to report the ongoing preclinical trial of xenotransplantation of microencapsulated pancreatic porcine islets in spontaneously diabetic dogs. Material and Methods Pig pancreas were digested with collagenase P and viable islets were isolated. They were precoated with alginate and calcium chloride, which results in a thin layer of cross-linked alginate surrounding each islet. Then they were microencapsulated with alginate/poli-lisine/alginate. Islets with a trypan blue viability count below 80% were discharged. Owners signed an informed consent and all the procedures were under revision of the ININCA’s Ethical Committee. The six dogs were in well health status and with diabetes mellitus of at least one year of evolution. All animals were being treated witn glargine insulin. The animals were 24hs-free of insulin treatment before the implantation. Under sedation microcapsules were implanted. Insulinemia basally and every-3 months and glycosiled hemoglobin basally and every-4 months were registered in peripheral blood. In the follow-up, the glycemia was registered twice a day, 3 hours after morning and night meals with blood glucose monitoring system. RESULTS The mean basal insuline dose was 10.4±7 IU vs. 8±6 seven days postimplantation (p=0.0093; two-tailed paired t test) showing a mean diminution of 23%. And the insuline needs were also reduced after a follow-up of 5 or 6 months (p<0.05). Animals who reached in their follow-up the glycolized hemoglobin control showed a decrease of 0.7 and 1.2%. All the owners subjectively claimed that their animals are now enjoying a better quality of life. DISCUSSION Insulinemia determinations confirmed the production of hormone from the implanted cells in receptors. Since this method cannot detect canine insulin, we hypothesized that this increase in hormone synthesis could be due to neogenesis from exocrine tissue microencapsulated with the islets, since purification ranged from 60 to 80 %. This could have important clinical implications if acinar tissue could facilitate the neogenesis and increase the insulino-independence time. The improvement in the reduction of insulin needs and in the metabolic control of these dogs suggest that xenotransplantation of porcine islets is a safe treatment without the risk of immunosuppression. Moreover, t he survival time of the graft suggests that one or two implants by year of encapsulated islets could be a way to obtain metabolic control.