Delivery of human adipose-derived stromal cells within <i>in situ</i> forming chitosan/PEG-PTMC hydrogels induces adverse outcomes in a femoral artery ligation model in athymic <i>nu/nu</i> mice
Bibliographic record
Abstract
Abstract The delivery of human adipose-derived stromal cells (hASCs) to ischemic tissues represents a promising strategy to promote vascular regeneration for patients with critical limb ischemia (CLI). Building on previous work, this study focused on the in vivo characterization of a hydrogel cell delivery platform for hASCs composed of peptide-functionalized methacrylated glycol chitosan (MGC-RGD) and a terminally acrylated triblock copolymer of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG(PTMC-A) 2 ) in athymic nu/nu mice with femoral artery ligation-induced critical limb ischemia (FAL-CLI). This immunodeficient mouse strain was selected to enable human cell transplantation in a model with conserved monocyte/macrophage function, recognizing that macrophages are key regulators of the biomaterial implant response, as well as vascular repair and regeneration. The hASCs were engineered to co-express tdTomato and firefly luciferase to enable longitudinal cell tracking using bioluminescence imaging (BLI). Interestingly, the hASCs were better retained following delivery in saline compared to hydrogel delivery. However, laser Doppler perfusion imaging (LDPI) analysis indicated that the restoration of hindlimb perfusion was similar between the two cell treatment groups. Critically, delivery of the hASCs within the hydrogels was associated with adverse outcomes only observed within this treatment group, including severe swelling, discoloration, and necrosis, which necessitated early euthanasia of some mice. CD45 staining supported that the combination of the cells and the hydrogels induced an inflammatory host response. These findings contrast with previous positive results when the platform was tested for hASC delivery in more severely immunocompromised NOD/SCID mice with FAL-CLI, as well as allogeneic rat ASC delivery in a healthy immunocompetent rat model. Overall, this study emphasizes the potential importance of testing cell delivery platforms in pre-clinical disease models that have retained host immune cell function, especially for immunomodulatory cell populations such as ASCs.
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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) | 0.001 | 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 | 0.001 |
| 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".