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
Bibliographic record
Abstract
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
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".