Advances in Cell Replacement Therapies for Diabetes
Bibliographic record
Abstract
Islet cell replacement therapies have evolved as a viable treatment option for type 1 diabetes complicated by problematic hypoglycemia and glycemic lability. Refinements of islet manufacturing, islet transplantation procedures, peritransplant recipient management, and immunosuppressive protocols allowed most recipients to achieve favorable outcomes. Subsequent phase 3 trials of transplantation of deceased donor islets documented the effectiveness of transplanted islets in restoring near-normoglycemia, glycemic stability, and protection from severe hypoglycemia, with an acceptable safety profile for the enrolled high-risk population. Health authorities in several countries have approved deceased donor islet transplantation for treating patients with type 1 diabetes and recurrent severe hypoglycemia. These achievements amplified academic and industry efforts to generate pluripotent stem cell-derived β-cells through directed differentiation for β-cell replacement. Preliminary results of ongoing clinical trials suggest that the transplantation of stem cell-derived β-cells can consistently restore insulin independence in immunosuppressed recipients with type 1 diabetes, thus signaling the profound progress made in generating an unlimited and a uniform supply of cells for transplant. Avoiding the risks of chronic immunosuppression represents the next frontier. Several strategies have entered or are approaching clinical investigation, including immune-isolating islets, engineering immune-privileged islet implantation sites, rendering islets immune evasive, and inducing immune tolerance in transplanted islets. Capitalizing on high-dimensional, multiomic technologies for deep profiling of graft-directed immunity and the fate of the graft will provide new insights that promise to translate into sustaining functional graft survival long-term. Leveraging these parallel progression paths will facilitate the wider clinical adoption of cell replacement therapies in diabetes care. ARTICLE HIGHLIGHTS: Transplantation of deceased donor-derived primary human islets has restored near-normoglycemia and protection from severe hypoglycemia in immunosuppressed recipients with type 1 diabetes. Transplantation of embryonic stem cell-derived β-cells has restored insulin independence in immunosuppressed recipients with type 1 diabetes. Clinical trials are underway and planned to evaluate the safety and efficacy of transplantation of mature stem cell-derived β-cells with transient, local, minimal, and/or no-maintenance immunosuppression in recipients with type 1 diabetes. The high-dimensional, multiomic monitoring of immunity to transplanted islets and of the fate of the islet graft will faciliate the identification of determinants of sustained islet graft function and of patients most likely to benefit from cell replacement therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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 teacher head, 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".