A Prevascularized Subcutaneous ‘Device-Lessʼ Site for Islet Transplantation.
Bibliographic record
Abstract
Cellular therapy is an attractive modality for diverse diseases including diabetes, Parkinson's, myocardial ischemia, single-gene liver defects and hyperparathyroidism. The availability of genetically engineered stem cells provides seemingly infinite possibilities for cellular replacement in regenerative medicine. Intrahepatic transplantation of insulin-secreting islets of Langerhans is a prototypic example of a highly successful cellular replacement therapy in patients with type 1 diabetes. As new stem-cell derived insulin-secreting cells become available, easily retrievable sites become an imperative priority as the safety profile of potentially teratogenic cell lines are defined in patients. As a consequence, intensified research has been dedicated to the pursuit of alternative transplant sites. Herein, we examined the ability of a new technique for ‘device-less' (DL) successful islet transplantation, through the temporary implantation of a medical angiocatheter. This approach harnesses the innate foreign body response in a favorable manner through transformation of a hitherto hypoxic and avascular subcutaneous space into a vascularized site. Succeeding a 3-6 week implant period, diabetic mice were transplanted with syngeneic islets into the subcutaneous DL space in parallel to recipients of islet renal subcapsular (KC) and subcutaneous alone transplants. Islets transplanted under the KC were able to reverse diabetes in 100% (n=10) of the recipients, whereas all diabetic recipients (n=10) transplanted with islets into the naïve subcutaneous space, failed to achieve normoglycemia. However, of DL recipients transplanted, diabetes reversed in 91.3% (n=23) of the recipients and maintained normoglycemia for over 100days. KC and DL recipients demonstrated similar glucose tolerance during a glucose challenge and the islet grafts stained for insulin. This study demonstrates the unprecedented ability to reverse diabetes by placing insulin-producing islets under the skin without need for a permanent device, matrix or exogenous growth factors. This technique may indeed be an appropriate surrogate for clinical islet engraftment leading to long-term islet and potential insulin producing stem cell graft function.Figure: No Caption available.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 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".