328.1: Preliminary results on the survival and maturation of stem-cell derived beta cells at different stages in a novel immunoprotective double encapsulation device
Notice bibliographique
Résumé
Background. Access to free human islet transplantation is currently restricted to a small portion of type 1 diabetic patients, mainly due to limited donor supply and the need of long-term immunosuppression. Islet encapsulation represents a promising alternative, but devices create a diffusion barrier that also limits graft vascularization and oxygenation. To address these issues, we developed a double encapsulation device where cells are encapsulated in high concentration alginate capsules and entrapped in a porous device to allow angiogenesis in vivo. The aim of this work was to test the capacity of our device to host vascularization in vitro and to assess the impact of our encapsulation process on the survival and maturation of stem-cell derived pancreatic cells at different stages. Methods. The porous part of our device was made of polyurethane using NaCl particles to control porosity. Cells were encapsulated by emulsion and internal gelation (Hoesli et al., 2011) in high-concentration alginate (5%) capsules previously shown to create a barrier to antibody penetration (Hoesli et al., 2012). Pseudo-islets (MIN6) were encapsulated in alginate capsules, mixed with a collagen solution containing Green Fluorescent Protein (GFP)-HUVECs and injected in the device. Devices were cultured for 5 days and HUVECs tube formation was assessed tracking GFP fluorescence. H1 human embryonic stem cells were differentiated towards beta cells following a 7-stage protocol described in the literature (Rezania et al., 2014; Balboa et al., 2022). Stage 4 (S4), S5 and S6 cells were encapsulated in alginate capsules. Cell viability was observed after 1 and 7 days after encapsulation (n=3). At S7 + 10 days, differentiation markers in S6 encapsulated cells were compared to free cells (n=1). Results. HUVECs cells formed tubes within our device after 5 days of culture in vitro. Ongoing transplantation experiments in C57BL/6 mice are going to probe whether this is reflected in vivo. No increase of cell death was observed when stem cell-derived pseudo-islets were encapsulated in alginate capsules at S5 and S6. However, we observed an increase of death when encapsulation occurred at S4. Preliminary data suggest that encapsulation of S6 cells increased the population of C-peptide+/NKX6.1+ cells in encapsulated cells compared to free cells (27.3 vs 21.1% at S7 + 10D, n=1). Conclusion. These promising preliminary results suggest that our double encapsulation device could (1) be properly vascularized providing sufficient oxygenation to encapsulated cells and (2) provide a 3D environment improving the differentiation/maturation of immature stem cell-derived beta cells. Diabète Canada. Fonds de Recherche du Québec - Santé. References: 1. Hoesli CA et al., Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation. Biotechnol Bioeng. 2011; 108(2):424-34 2. Hoesli CA et al., Reversal of diabetes by βTC3 cells encapsulated in alginate beads generated by emulsion and internal gelation. J Biomed Mater Res B Appl Biomater. 2012; 100(4):1017-28. 3. Rezania A et al., Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014; 32(11):1121-33 4. Balboa D et al., Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Nat Biotechnol.2022; 40(7):1042-1055
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».