Development of a three-dimensional microenvironment and dielectric monitoring system for long-term «in vitro» culture and differentiation of human pancreatic islets
Bibliographic record
Abstract
Human pancreatic islet transplantation presents an attractive method for type I diabetes cellular therapy. However, there remain several limitations that should be addressed in order to increase the efficacy of the transplantation procedure; the most important of which are addressing the shortage of available pancreatic tissue and the viability of post-isolation islets. These obstacles are overcome through methods directed at long-term in vitro preservation, culture, and expansion of post-isolation islets in order to arrive at functionally viable islet populations for transplantation purposes. This thesis presents a novel system that promotes in vitro human pancreatic islet preservation and culture in a controlled microenvironment that is monitored noninvasively. The development of this system is accomplished in four consecutive stages: i) optimization of a two-dimensional surface-modified extracellular matrix (ECM) substrate, ii) fabrication of a geometrically controlled and interconnected scaffold suitable for islet culture, iii) three-dimensional in vitro culture incorporating the optimized ECM components and fabricated scaffold, and iv) incorporating the three-dimensional microenvironments within a multi-welled perfusion bioreactor, coupled with dielectric measurement electrodes, for the long-term in vitro culture of human pancreatic islets. Several novelties attributed to the developed system are also presented. The two-dimensional studies revealed fibronectin to enhance glucose-dependent insulin functionality and morphology, while collagen I/IV contribute to adhesion. The microfabricated Poly(lactic-co-glycolic acid) (PLGA) scaffolds were constructed to give suitable pore structures and full interconnectivity, in a reproducible geometrically controlled manner. Furthermore, the incorporation of the optimized ECM components into the scaffolds was accomplished through islet embedding in an ECM laden gel that is seeded within the microfabricated scaffold pore structures. The three-dimensional microenvironment encouraged long-term human islet culture, giving high insulin release indices of ~1.8, while increasing islet gene expression. Finally, a fabricated multi-well perfusion bioreactor, equipped with an electrical impedance dielectric spectroscopy monitoring system, was employed in the controlled three-dimensional culture of the isolated islets. This system was successful in the long-term monitoring of human pancreatic islet differentiation and redifferentiation in a controlled three-dimensional microenvironment, yielding a population that is characteristically, morphologically, and functionally analogous to freshly isolated islets.
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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 | 0.001 | 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".