Adipose-Derived Stem Cells in a Resilient <i>In Situ</i> Forming Hydrogel Modulate Macrophage Phenotype
Why this work is in the frame
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Bibliographic record
Abstract
Injectable hydrogels have the potential to enhance stem cell-based therapies by improving cell localization, retention, and survival after transplantation. The inflammatory response to both the hydrogel and the encapsulated cells is a critical aspect of this strategy, with macrophages being highly involved in the process of hydrogel remodeling, angiogenesis, and tissue regeneration. As a step toward the development of a cell-based strategy for therapeutic angiogenesis, this work compared the intramuscular injection of allogeneic rat adipose-derived stem/stromal cells (rASCs) in an in situ gelling hydrogel with the injection of the hydrogel alone and rASCs in saline in an immunocompetent rat model by immunohistochemical analysis over 4 weeks. rASCs delivered in the hydrogel were retained intramuscularly at significantly higher densities as compared with cells delivered in saline. The encapsulated rASCs modulated the inflammatory response, promoting CD68 + macrophage recruitment, with the majority of infiltrating cells expressing the M1 marker CCR7, as well as a higher fraction of CD163 + M2c macrophages surrounding the hydrogel. Furthermore, rASCs reduced the initial expression of inducible nitric oxide synthase and promoted arginase-1 expression in the infiltrating macrophages over time, consistent with a shift toward a more proregenerative phenotype. Coincident with the enhanced macrophage infiltration, significantly more CD31 + lumens were observed surrounding and within the hydrogels with rASCs at 2 and 4 weeks as compared with the hydrogels alone. Overall, these results are a promising indication that encapsulated rASCs can have immunomodulatory effects and may enhance angiogenic processes after intramuscular injection, promoting a regenerative macrophage response and blood vessel formation.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 | 0.001 |
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 it