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: Takayuki Tanaka, Minoru Fujita, Rita Bottino, Jon D Piganelli, Kevin McGrath, Jiang Li, Whayoung Lee, Hayato Iwase, Martin Wijkstrom, Suzanne Bertera, Cassandra Long, Douglas Landsittel, Ken Haruma, David K C Cooper, Hidetaka Hara
• Journal: Islets (Islets) Vol. 8 Issue 1 Pg. 1-12 ( 2016) ISSN: 1938-2022 [Electronic] United States
• PMID: 26857703 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants

Topics

• Animals
• Animals, Inbred Strains
• Antioxidants (pharmacology)
• Biopsy
• Cell Proliferation (drug effects)
• Cells, Cultured
• Diabetes Mellitus, Type 1 (surgery)
• Disease Models, Animal
• Early Diagnosis
• Endoscopy, Digestive System
• Graft Rejection (diagnosis, pathology, prevention & control)
• Humans
• Immunosuppression Therapy
• Islets of Langerhans (cytology, drug effects, pathology)
• Islets of Langerhans Transplantation (adverse effects)
• Leukocytes, Mononuclear (cytology, drug effects)
• Oxidative Stress (drug effects)
• Stomach
• Swine
• Swine, Miniature
• Tissue Culture Techniques
• Transplantation, Heterotopic (adverse effects)