TransEndoscopic Gastric SubMucosa Islet Transplantation (eGSM-ITx) in pigs with streptozotocine induced diabetes - technical aspects of the procedure - preliminary report.
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 caused not only by immunological reactions but also due to the site of grafting and IBMIR. Gastric submucosal space could be an alternative site for transplantation. The aim of this study was to assess the possibility of endoscopic islets transplantation into the gastric submucosa-its efficacy and potential complications.<br />


METHODS
20 Landrace pigs weighing 19-24 kg were obtained for the study. Seven animals were controls (C-group) and 13 formed the transplantation group (TX group). In both groups diabetes was induced by streptozotocine (stz) infusion at a dose of 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 anaesthesia in pigs with diabetes and to study the influence of basiliximab infusion on pigs, in the Tx-group to perform endoscopic submucosal islet transplantation (eGSM-ITx). Immunosuppression consisted of tacrolimus 0.2 mg/kg and sirolimus 6 mg/m(2). At 7 days post transplantation, control gastroscopy was performed to assess the gastric mucosa and to obtain biopsies for histopathology. 10 to 30 days after eGSM-ITx, magnetic resonance (MRI) scan was performed. Stomach and pancreas were obtained at autopsy for histopathology. Glycemia was assessed twice daily during the experiment. 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.<br />


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+/-3170 IEQ/kg. Tx-group animals had a significantly lower insulin requirement and significantly lower mean glycemia since the first day post transplantation. C-group animals all required insulin once daily to keep glycemia below 600 mg/dl. There were no signs of perforation, ulceration or bleeding after eGSM-ITx on gastroscopy and histopathological examination. MRI scans revealed unspecific thickening of gastric wall at sites of islet deposition.<br />


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.<br /> <br /> <br />
Wszola
Michal
M
Department of General and Transplantation Surgery, Warsaw Medical University, Poland. michal.wszola@wp.pl
Berman
Andrzej
A
Fabisiak
Michal
M
Domagala
Piotr
P
Zmudzka
Magdalena
M
Kieszek
Rafal
R
Perkowska-Ptasinska
Agnieszka
A
Sabat
Marek
M
Pawelec
Krystian
K
Kownacki
Lukasz
L
Piotrowska-Kownacka
Dorota
D
Ostrowski
Krzysztof
K
Januchta
Monika
M
Klucinski
Włodzimierz
W
Rowinski
Olgierd
O
Kwiatkowski
Artur
A
Chmura
Andrzej
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077552:Basiliximab; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005260:Female; D005753:Gastric Mucosa / Q000601:surgery*; D005773:Gastroscopy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013552:Swine
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab