235.7: Analysis of collagenase dose on allogeneic islet isolation outcomes and glucose-stimulated insulin release
Notice bibliographique
Résumé
Introduction: The use of a low collagenase dose has been previously reported as potentially being beneficial to allogeneic islet isolation outcomes and specifically the glucose-stimulated insulin response (GSIR). In this study, the effect of the low collagenase dose on islet isolation and insulin secretion is expanded to investigate the role of the enzyme type and non-collagenolytic components. Methods: Clinical islet isolations were performed utilizing standard-of-care protocols between Jul 2008 and Mar 2023. Pancreases were perfused with an enzyme blend of either a non-targeted Liberase MTF high collagenase dose with thermolysin (HD-MTF, n= 441), a targeted (<20 WU/g) Liberase MTF low collagenase dose with thermolysin (LD-MTF, n=41) or a targeted (<20 WU/g) rCollagenase HI with BP Protease low collagenase dose (LD-rHI, n=93). Dynamic GSIR testing was performed at the time of the islet transplant using approximately 100 IE. Islets were exposed to 16 min intervals of low glucose (2.3 mMol) and high glucose (23.0 mMol) following a 60 min stabilization period. Perfusate was collected and analyzed for insulin concentrations. Perifusion samples were collected, and islets were stained with dithizone, and quantified to normalize the raw insulin values. Stimulation indexes are reported as both peak to baseline as well as the area under the curve. Basal and stimulated metabolic rates were calculated to express the final islet product insulin secretion. Results: In comparing some critical donor parameters across all groups (Table 1), HD-MTF had a significantly longer cold ischemia time and smaller pancreas than LD-MTF. The use of LD-rHI had a notably higher purification recovery despite pre-purification trapped proportions being similar between groups. Islet yields at all time points of processing showed comparable results, however, LD-rHI had a higher percentage of islet preparations proceed to transplant than LD-MTF.In assessing GSIR data (Table 2), the low-dose test groups both had higher stimulated responses to glucose than the high-dose control group, however, only the LD-rHI group was statistically higher. There was no observed difference between the 2 low dose groups. Both the raw and normalized stimulated insulin secretion levels were significantly higher in LD-rHI vs the HD-MTF.Conclusions: The use of a low-dose collagenase is associated with improved islet isolation parameters as well as insulin secretion in response to high glucose and can effectively and reliably lead to improved islet isolation outcomes in comparison to the high-dose strategy. The results were similar when comparing the type of enzyme used with a low-dose protocol. However, there was an improved purification recovery and transplant success rate observed. Only the LD-rHI group showed statistical improvement on the standard high-dose approach when assessing insulin secretion. This could be a result of utilizing BP protease instead of Thermolysin as the non-collagenolytic component.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».