TRANSPLANTATION OF MICROENCAPSULATED PANCREATIC ISLETS IN NONIMMUNOSUPPRESSED DIABETIC RECIPIENTS.
Notice bibliographique
Résumé
P449 Aims: We aimed to bring our microencapsulated islet transplant system into human pilot clinical trials. To achieve this goal, we have addressed and thoroughly fulfilled a number of safety and efficacy issues, as far as both, chemical formulation and physics of the microcapsules, and the whole product (islets in microcapsules) were concerned, either in vitro or in vivo, post-transplant into pre-clinical animal models of diabetes. Methods: a) Microcapsules - Na alginate (AG), prevalently composed of mannuronic acid, underwent stepwise, multiple purification and ultrafiltration process, in order to remove endotoxins as well as other pyrogens and foreign microparticles. Poly-L-ornithine (PLO), at low molecular weight, as uniquely shown by our laboratory, was used to coat the initially formed AG gel beads. The latter, upon previous, careful mixing with the islet suspension, were obtained by a microdroplet generator, not involving use of electrostatic forces, but simply air shears and mechanical pressure; b) Islets – we separated/purified islets from the pancreas of either neonatal pigs (NPCC), or humans, by the classical collagenase digestion and COBE 2991 gradient purification, according to protocols developed by the Edmonton group, University of Alberta, Canada. The isolated islets were culture-maintained in HAM F12 for at least 24 hrs., prior to encapsulation, and underwent both morphologic (integrity, viability and immunocytochemistry) and functional (in vitro glucose stimulated insulin release) quality control testing; c) Experimental design – nonimmunosuppressed NOD mice and dogs with spontaneous, insulin-dependent diabetes were enrolled in the pre-clinical trials and were grafted intraperitoneally with microencapsulated either NPCC (NOD mice, dogs) or human (NOD) islets, with the post-TX blood glucose levels as well as daily insulin consumption rates being carefully monitored. Results: Our method resulted in endotoxin-free, highly purified AG. AG/PLO empty microcapsules did not provoke any inflammatory cell reaction upon intraperitoneal TX in NOD mice, with the microcapsules retaining full morphologic integrity and mechanical strenght, and containing viable islet cells. The transplanted NOD mice, with either human or NPCC encapsulated islets showed full remission of hyperglycemia that was sustained for at least 60 throughout 180 days. Transplanted dogs with NPCC showed remission of hyperglycemia coupled to substantial evidence of peripheral serum porcine C-peptide levels. Exogenous insulin withdrawal was achieved in one animal for 50 days, while its prolonged and sustained reduction was accomplished in all recipients. Conclusions: We have provided evidence that microencapsulated islets may represent a safe tool for transplantation with no recipient’s pharmacological immunosuppression. In vitro and preliminary in vivo pre-clinical results have warranted us permission, from the Italian Ministry of Health to embark on clinical trials of microencapsulated human islet allografts tha now are ready to begin.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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) | 0,002 | 0,000 |
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 ».