Endoscopic biopsy of islet transplants in the gastric submucosal space provides evidence of islet graft rejection in diabetic pigs. Islets 2016;8(1):1-12
Date
02/10/2016Pubmed ID
26857703Pubmed Central ID
PMC4878262DOI
10.1080/19382014.2016.1149283Scopus ID
2-s2.0-84968542318 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Tanaka T, Fujita M, Bottino R, Piganelli JD, McGrath K, Li J, Lee W, Iwase H, Wijkstrom M, Bertera S, Long C, Landsittel D, Haruma K, Cooper DK, Hara HAuthor
Whayoung Lee MD Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Inbred Strains
Antioxidants
Biopsy
Cell Proliferation
Cells, Cultured
Diabetes Mellitus, Type 1
Disease Models, Animal
Early Diagnosis
Endoscopy, Digestive System
Graft Rejection
Humans
Islets of Langerhans
Islets of Langerhans Transplantation
Leukocytes, Mononuclear
Oxidative Stress
Stomach
Swine
Swine, Miniature
Tissue Culture Techniques
Transplantation, Heterotopic