14-4: INVESTIGATING THE SUBCUTANEOUS SPACE AS AN ALTERNATIVE TRANSPLANT SITE FOR ISLET TRANSPLANTATION
Bibliographic record
Abstract
Introduction: In Type 1 diabetes (T1D), beta-cell-specific autoimmune destruction leads to lifelong exogenous insulin dependence. The hepatic portal vein is the preferred site for islet transplantation; however, high flow rates and instant blood-mediated inflammatory reaction present a risk for islet graft attrition creating the need for alternative islet transplantation sites that are highly vascularized and can elicit immunoprotection. Previous studies demonstrated that subcutaneous catheter implantation into mice elicits a foreign body response resulting in a vascularized pocket to support islet engraftment; however translatability into non-obese diabetic (NOD) mice, a spontaneous model of T1D, has not been explored. We hypothesize that subcutaneous transplantation of islets into a prevascularized pocket will restore normoglycemia in NOD mice. Methods: C57BL/6, NOD.Rag, and NOD mice were implanted with 2cm 6-Fr nylon catheters for 4-weeks to generate a pre-vascularized subcutaneous transplant site. The catheter was removed from streptozotocin-induced diabetic mice and transplanted with 250 or 500 syngeneic islets subcutaneously or under the kidney capsule. Engraftment was monitored by blood glucose and graft function was measured by intraperitoneal glucose tolerance test. Results: Subcutaneous implantation of the catheter into C57BL/6 mice resulted in the formation of a vascularized pocket, as evident by CD31 expression and restoration to normoglycemia. Syngeneic islet transplants under the kidney capsule restored normoglycemia within 24hrs in all mice. In the subcutaneous transplant site, we observed delayed engraftment in NOD.Rag recipients and failed engraftment in NOD recipients, suggesting a lack of necessary vascularization factors for proper engraftment. Conclusions: Subcutaneous transplantation of islets into a modified pre-vascularized space restored normoglycemia in C57BL/6 mice. Modifications to the subcutaneous site are needed to support islet graft function in NOD strains. Future studies will investigate how differences in the immunological response to the islet graft vary between the kidney capsule and subcutaneous transplant site of C57BL/6 and NOD mice.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".