title: Endoscopic biopsy of islet transplants in the gastric submucosal space provides evidence of islet graft rejection in diabetic pigs.
abstract: Transplantation of islets into the gastric submucosal space (GSMS) has several advantages (e.g., avoidance of the instant blood-mediated inflammatory response [IBMIR], ability to biopsy). The aim of this study was to determine whether endoscopic biopsy of islet allografts transplanted into the GSMS in diabetic pigs can provide histopathological and immunohistochemical information that correlates with the clinical course (e.g.,, blood glucose level, insulin requirement). Islet allografts (Group1: 10,000 kIEq /kg [n = 4]; Group2: 15,000 kIEq /kg [n = 2]) were transplanted into the GSMS of diabetic pigs under immunosuppression. In Group2, the anti-oxidant, BMX-001 was applied during preservation, isolation, and culture of the islets, and at the time of transplantation. Endoscopic biopsies of the islet grafts were obtained one or 2 weeks after transplantation, and histopathological features were compared with the clinical course (e.g., blood glucose, insulin requirement). In Group1, in the absence of anti-oxidant therapy, most of the islets became fragmented, and there was no reduction in exogenous insulin requirement. In Group2, with an increased number of transplanted islets in the presence of BMX-001, more healthy insulin-positive islet masses were obtained at biopsy and necropsy (4 weeks), and these correlated with reductions in both blood glucose level and insulin requirement. In all cases, inflammatory cell infiltrates were present. After islet transplantation into the GSMS, endoscopic biopsy can provide information on graft rejection, which would be an immense advantage in clinical islet transplantation.
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Takayuki
authors: T
authors: Tanaka
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.|e Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School , Kurashiki , Japan.
authors: Minoru
authors: M
authors: Fujita
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.|b Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Rita
authors: R
authors: Bottino
authors: b Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Jon D
authors: JD
authors: Piganelli
authors: c Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Kevin
authors: K
authors: McGrath
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Jiang
authors: J
authors: Li
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Whayoung
authors: W
authors: Lee
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Hayato
authors: H
authors: Iwase
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Martin
authors: M
authors: Wijkstrom
authors: b Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Suzanne
authors: S
authors: Bertera
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Cassandra
authors: C
authors: Long
authors: d Biostatistics and Clinical and Translational Science, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Douglas
authors: D
authors: Landsittel
authors: e Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School , Kurashiki , Japan.
authors: Ken
authors: K
authors: Haruma
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: David K C
authors: DK
authors: Cooper
authors: a Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh , Pittsburgh , PA , USA.
authors: Hidetaka
authors: H
authors: Hara
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D000975:Antioxidants / Q000494:pharmacology; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004195:Disease Models, Animal; D042241:Early Diagnosis; D016145:Endoscopy, Digestive System; D006084:Graft Rejection / Q000175:diagnosis* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013270:Stomach; D013552:Swine; D013556:Swine, Miniature; D046509:Tissue Culture Techniques; D016042:Transplantation, Heterotopic / Q000009:adverse effects*
chemical_list: D000975:Antioxidants
keywords: anti-oxidant; biopsy; endoscopy; gastric submucosal space; islets; pig; transplantation