Technique of Endoscopic Biopsy of Islet Allografts Transplanted into the Gastric Submucosal Space in Pigs

Abstract

Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet Tx into the gastric submucosal space (GSMS) can be performed endoscopically, and has the potential advantage of histological evaluation by endoscopic biopsy. The aim of this study was to determine whether a representative allograft sample could be obtained endoscopically. We performed islet Tx into the GSMS in non-immunosuppressed pigs using simple endoscopic submucosal injection. Islets were transplanted at 4 sites. Endoscopic ultrasonography and biopsy of the transplanted islets at 2 sites by modified endoscopic submucosal dissection were carried out successfully in all pigs 5 days after islet Tx. Tissue obtained at both biopsy and necropsy (including full-thickness sections of the gastric wall around the sites of the remaining islets and biopsies) were examined by histology and immunohistochemistry to confirm the presence of the islet grafts and any features of rejection. Representative allograft sampling was successfully obtained from all biopsy sites. All biopsies included islets with insulin-positive staining. There was significant CD3+ and CD68+ cell infiltration in the islet masses obtained at biopsy and from sections taken at necropsy, with similar histopathological features. Endoscopic biopsy of islet allografts in the GSMS is feasible, provides accurate histopathological data, and would provide a significant advance if translated into clinical practice.

Endoscopic biopsy of islet transplants in the gastric submucosal space provides evidence of islet graft rejection in diabetic pigs

“…We previously established the technique of endoscopic biopsy after islet transplantation into the GSMS in non-diabetic pigs not receiving immunosuppressive therapy. 5 Tissue obtained at both biopsy and necropsy 5 d after transplantation showed similar histological features of rejection. These results indicated that endoscopic biopsy of islet allografts in the GSMS is feasible, and provides accurate histopathological data.…”

“…Under inhalational anesthesia, islets (in culture medium C/¡ 17 mM BMX-001) were transplanted into the GSMS at 4 (Group1) or 7 (Group2) sites endoscopically via submucosal injection (GIF-2T160, Olympus Medical Systems, Center Valley, PA). 5…”

“…4 In addition, islet transplantation into the GSMS by an endoscopic approach offers several advantages compared to the portal vein in the form of reduced technical complications and potential ability to biopsy. 5 Monitoring for islet graft survival and rejection would be an immense advantage. Following intraportal islet transplantation, histological assessment of the allograft cannot be reliably obtained.…”

Recent advances in understanding xenotransplantation: implications for the clinic

“…Overcoming this barrier is proving difficult, although genetic modification of the pigs may prove helpful [61]. An alternative would be the transplantation of the islets in sites other than the liver, such as the gastric submucosal space, where the islets are not immediately exposed directly to blood, but still receive a good supply of oxygen and nutrients [62,63]. An ideal site should feature portal delivery of insulin, but be accessible by a minimally-invasive procedure associated with minimal complications.…”

Translational Molecular Imaging of Diabetes

“…This study showed that the striated muscle could be a promising site for islet transplantation that promotes full revascularization of Curr Radiol Rep (2013) 1:205-215 209 implanted grafts. Besides the forearm muscle, several other islet transplantation sites including the gastric submucosal space [80,81] and adrenal glands [82] have also been investigated. Clearly, non-invasive imaging could greatly assist in evaluating these sites and in monitoring islet survival aiding to clinical translation of these new approaches.…”