Endoscopic Gastric Submucosal Transplantation of Islets (ENDO-STI): Technique and Initial Results in Diabetic Pigs

Abstract

The results of transplantation of human donor islets into the portal vein (PV) in patients with diabetes are encouraging. However, there are complications, for example, hemorrhage, thrombosis and an immediate loss of islets through the 'instant blood-mediated inflammatory reaction' (IBMIR). The gastric submucosal space (GSMS) offers potential advantages. Islets were isolated from adult pigs. Recipient pigs were made diabetic by streptozotocin. Donor islets were injected into the GSMS through a laparotomy (Group 1A, n = 4) or endoscopically (Group 1B, n = 8) or into the PV through a laparotomy (Group 2, n = 3). The pigs were followed for a maximum of 28 days. Monitoring of C-peptide in Group 1 indicated that there was minimal immediate loss of islets whereas in Group 2 there was considerable loss from IBMIR. In Group 1, there were significant reductions in mean blood glucose and mean exogenous insulin requirement between pretransplantation and 20 days posttransplantation. In Group 2, there was no significant reduction in either parameter. Insulinpositive cells were seen in the GSMS in Group 1, but not in the liver in Group 2. Endoscopic gastric submucosal transplantation of islets (ENDO-STI) offers a minimally invasive and quick approach to islet transplantation, avoids IBMIR and warrants further exploration.

Update on Islet Transplantation

“…In a mouse model, syngeneic rodent islets transplanted into the femur are able to reverse hyperglycemia without any evidence of derangement of the hematopoietic system or disruption of structural integrity (Cantarelli et al 2009). Another promising site is the gastric submucosal space (GSMS) (Echeverri et al 2009;Wszola et al 2009). After endoscopic placement, islets would benefit from a rich blood supply and a high oxygen tension.…”

“…After endoscopic placement, islets would benefit from a rich blood supply and a high oxygen tension. Preclinical trials using a porcine model showed reduced early islet loss and insulin requirements when GSMS islets were compared to intraportal islets (Echeverri et al 2009). …”

Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets

“…The feasibility of MR imaging of transplanted islets in a clinical situation was assessed by in vivo imaging of islet engraftment in a swine model. Because swine islets are rapidly destroyed during transplantation (22), the recipient swine was treated with immunosuppressive drugs (23). The transplantation was then performed by an interventional radiologist (24).…”

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.…”