07-2: A PERFUSABLE ENCAPSULATION DEVICE SCALED FOR CLINICALLY RELEVANT THERAPEUTIC ISLET DOSES SHOWS RAPID INSULIN RESPONSE IN VITRO AND ACUTE SAFETY IN PIG TRANSPLANTATION MODEL
Bibliographic record
Abstract
Introduction: Type 1 Diabetes results from autoimmune destruction of pancreatic beta cells, leading to insulin deficiency and hyperglycemia. Islet transplantation can restore insulin production and eliminate the need for exogenous insulin in many recipients for several years. However, widespread use is hindered by donor scarcity, poor cell engraftment, and the need for lifelong immunosuppression. Encapsulation protects islets from immune rejection but restricts nutrient supply, leading to graft cell loss. We aim to develop a vascularized encapsulation device to improve nutrient and oxygen delivery, enhancing islet survival and function. Methods: Single- and 9-channel encapsulation devices were fabricated using sacrificial lattice 3D printing, polymer coating, and autoclaving, followed by aseptic filling of cells in alginate. The devices were tested with mouse insulinoma 6 beta cells and pluripotent stem cell-derived islets. Functionality was assessed by perfusing glucose-containing media through the device inlet while monitoring insulin secretion. Viability and insulin secretion were measured over 10 days of perfusion culture to evaluate continuous nutrient delivery. Devices designed to accommodate clinically relevant islet doses were surgically implanted in pigs with device patency and inflammatory responses monitored. Results: Mouse insulinoma 6 beta cells showed rapid insulin secretion in response to a step change glucose stimulation applied to the infusion through the device inlet. The device enabled stem cell-derived islets(1) maturation, maintaining over 90% viability during the 10-day perfusion period. In pigs, no major adverse events occurred post-implantation. No signs of acute inflammation, infection or fibrosis were observed. Except for some early kinking, the devices maintained their structural integrity, suggesting feasibility for in vivo application. Conclusions: This study describes a novel vascular lattice graft for diabetes cellular therapy. Future work will focus on optimizing vascular-device geometries and evaluating therapeutic efficacy in diabetic models. Combining stem cell-derived islets with a perfused immunoprotective system approach holds promise for progress in long-term diabetes treatment.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".