“IMPROVING AVAILABILITY OF HUMAN ISLET CELLS FOR CLINICAL TRANSPLANTATION IN TYPE 1 DIABETES”
Bibliographic record
Abstract
O381 Aims: Islet transplantation is constrained by limited donor resource. Improving islet isolation yields from donor pancreas is crucial for scaling up clinical islet transplantation. We report a strategy for improving the availability of islets by subjecting tissue to in vitro culture and secondary purification of impure pancreatic tissue. Methods: Since January 2003, 27 consecutive human pancreases from multi-organ donors were processed for islets. The initial 9 consecutive organs(Group I) were processed using a standard protocol: intraductal collagenase perfusion, continuous digestion and dissociation, and density gradient purification. In the subsequent 18 processes(Group II), purified islets and the impure tissue left over from initial purification were cultured at 22°C for 12-36 hours, then the impure tissue was re-purified using standard purification in an attempt to recover more islets. Islet viability was assessed by insulin secretion in-vitro after incubation in 2.8 vs. 20mM glucose. Islets were infused to the liver of type I diabetic recipients in a procedure of percutaneous trans-hepatic portal cannulation. Patients receive 1 to 3 islet infusions until 10,000 IE(islet equivalent to 150μm in diameter)/kg body Wt. are provided. Results: In Group I, each pancreas yielded 214,109±53184 IE (Mean±SE) with a purity of 75.6±6.2% and recovery of 58.2±7.5% from pre-purification islet count. In Group II, primary purification produced 326,095±37,976 IE (NS, compared with Group I). Re-purification of impure tissue recovered an additional 121,198±21,760 IE. Yields from both purifications totalled 447,293±48,145 IE (vs. Group I, p<0.01), with an overall purity of 70.5±2.4% and recovery of 73.2±4.4 post-purification. The islet recovery after 12 to 36 hours culture at 22°C was 92.5±4.0%. At in vitro viability tests, islets demonstrated 3 fold insulin secretion in response to static glucose stimulation with no differences between primary and secondary purified islets. According to the minimum graft requirement, only 4 of 9 Group I islet preparations were transplanted. Comparatively, 16 of 18 pancreas preparations in Group II resulted in transplant, and the rate would be 7 of 18 if secondary purification were not performed. Since March, 2003, 9 type I diabetic patients received 1 to 3 islet infusions. Seven have achieved insulin independence. Two awaiting additional transplant retain islet graft function with significantly reduced insulin requirement. Conclusions: Islet preparation protocols with in vitro culture and secondary purification significantly augment islet yields and improve the rate of islet availability for clinical transplantation, without compromising islet graft purity and viability.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".