Mesenchymal Stem Cells Reduce Inflammation while Enhancing Bacterial Clearance and Improving Survival in Sepsis
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
RATIONALE: Sepsis refers to the clinical syndrome of severe systemic inflammation precipitated by infection. Despite appropriate antimicrobial therapy, sepsis-related morbidity and mortality remain intractable problems in critically ill patients. Moreover, there is no specific treatment strategy for the syndrome of sepsis-induced multiple organ dysfunction. OBJECTIVES: We hypothesized that mesenchymal stem cells (MSCs), which have been shown to have immunomodulatory properties, would reduce sepsis-induced inflammation and improve survival in a polymicrobial model of sepsis. METHODS: Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of MSCs or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage fluid and tissues were collected for analyses. Longer-term studies were performed with antibiotic coadministration to assess the effect of MSCs on survival. MEASUREMENTS AND MAIN RESULTS: MSC treatment significantly reduced mortality in septic mice receiving appropriate antimicrobial therapy. MSCs alone reduced systemic and pulmonary cytokine levels in mice with CLP-induced sepsis, preventing acute lung injury and organ dysfunction, despite the low levels of cell persistence. Microarray data highlighted an overall down-regulation of inflammation and inflammation-related genes (such as IL-10, IL-6) and a shift toward up-regulation of genes involved in promoting phagocytosis and bacterial killing. Finally, bacterial clearance was significantly greater in MSC-treated mice, in part due to enhanced phagocytotic activity of the host immune cells. CONCLUSIONS: These data demonstrate that MSCs have beneficial effects on experimental sepsis, possibly by paracrine mechanisms, and suggest that immunomodulatory cell therapy may be an effective adjunctive treatment to reduce sepsis-related morbidity and mortality.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it