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Islet size affects engraftment but not functionality in pancreatic islet transplantation

Daria Zorzi, Tammy Phan, Yong Lin, Luca Cicalese, Cristiana Rastellini

Department of Surgery, Texas Transplant Center, University of Texas Medical Branch, Galveston, TX, United States

Background: Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression. However, optimization and standardization of protocols are still needed to improve success. Many areas have been investigated including morphologic characterization of the graft to determine best islet size for optimal engraftment and functionality.

Material and Methods: Pancreatic islets were isolated from 9-12 weeks old C57/BL10 male mice using standard and overdigestion techniques. Islets were separated by size in three different groups using stainless steel mesh filtrations (150µm and 300 µm). Islet size was then confirmed through observation at light microscopy and islets were counted and divided for ITX in 3 groups: small (<150 µm), medium (150-300 µm), and large (>300 µm). Streptozotocin induced diabetic syngeneic recipients received 600, 400, and 200 Islet Equivalent under the kidney capsule for each size. Controls received ITX for each isolation without dividing the islet per size. Animals were monitored for blood glucose level, and body weight. Time of diabetes reversal was reported as early, late (10 and 20 days post-TX) and no reversal. In reversed animals, islet functionality was assessed by multiple intra-peritoneal glucose tolerance tests (IPGTT).

Results: Small islets reversed diabetes in 100% of the animals regardless of the mass (most of them within 7 days post-ITX) and performed significantly better than medium and large islets (table). No significant difference was observed in IPGTT results from all animals that reversed diabetes (early or late).

Conclusion: This data suggest that small islets are superior in engraftment even when organs are slightly over digested. When islets are engrafted, functionality doesn’t seem to be affected by size. This suggests that clinical isolations should be standardized on obtaining smaller islets.