Transendoscopic islet transplantation to gastric submucosa (eGSM-ITX) of pigs with streptozotocine induced diabetes – preliminary results
M Wszola, A Berman, M Fabisiak, R Kieszek, M Zmudzka, P Domagala, A Perkowska-Ptasinska, K Pawelec, M Sabat, L Kownacki, K Ostrowski, L Gorski, A Wernikowski, W Klucinski, O Rowinski, L Paczek, A Kwiatkowski, A Chmura
Ann Transplant 2009; 14(1): 46-46
Background: Islets and pancreas transplantation have become standard treatments of patients with diabetic complications. However pancreas transplantation is associated with high incidence of complications and the long-term results of islet transplantation are still unsatisfactory. Loss of pancreatic islets grafts is not only caused by immunological reactions but also due to the site of grafting and IBMIR. Gastric submucosa might be an alternative site for transplantation. The aim of this study was to assess the possibility of endoscopic islets transplantation into the gastric submucosa.
Material/Methods: 20 Landrace pigs weighing 19-24 kg were obtained for the study.7 animals were controls(C-group)and 13 were Transplantation group(TX group). In both groups diabetes was induced by streptozotocine (stz) infusion at 200 mg/kg. At 7 days post stz infusion pigs of both groups underwent endoscopy-in group-C to assess the feasibility of gastroscopic examination under general anesthesia in pigs with diabetes and in Tx-group to perform eGSM-ITx. Immunosuppression consisted of tacrolimus,sirolimus. At 7 days post transplantation, control gastroscopy was performed to assess the gastric mucosa and to take biopsies for histopathology. 10 to 30 days after eGSM-ITx Magnetic Resonance(MRI) examination was performed and pigs were euthanized. Stomach and pancreas were obtained at autopsy for histopathology. For 10 days after diabetes induction (up to three days after eGSM-ITx)in both groups, insulin was given to reach glycemia between 150-200 mg/dl,after that period insulin was given only when glycemia exceeded 600 mg/dl.
Results: There were no differences in insulin requirement and glycemia up to the day of eGSM-ITx between the groups. Tx-group animals received a mean of 6000 IEQ/kg. Tx-group animals had a significantly lower insulin requirement and significantly lower mean glycemia since the first day post transplantation. This trend was observed till the end of study at 1 month. Beginning at day 4 post eGSM-ITx pigs from the ITx-group did not receive insulin. There were no signs of perforation, ulceration or bleeding after the eGSM-ITx on gastroscopy and histopathological examination. In MRI scans unspecific thickening of gastric wall was observed at sites of islet deposition.
Conclusions: Transendoscopic islets transplantation into gastric submucosa is feasible and a safe procedure in an experimental animal setting. Its potential for clinical application in human subjects needs further studies.