268. Human Mesenchymal Stem Cells Augment Neutrophil Function to the Human Fungal Pathogen, <i>Candida albicans</i>
Bibliographic record
Abstract
Abstract Background Neutrophils are critical innate immune cells that play a crucial role in protection against invading pathogens. Mesenchymal stem cells (MSC) are multipotent progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes and possess immunomodulatory effects. MSC are the focus of clinical investigation in various comorbidities, including diabetes, cancer, and invasive infections. Methods Human MSC were derived from bone marrow and have been characterized to meet all criteria of MSC (ISCT guideline). Cells were seeded at 100,000 cells per well in fibronectin (50ug/mL)-coated 24-well plate and incubated for 24 hours at 37°C, 5% CO2. The next day, 0.5 mL of whole blood from three healthy donors was added for another 24 hours, after which the neutrophils were isolated, viability measured, and a high throughput multiparametric neutrophil function assay was performed, compared to non-MSC exposed neutrophils (control neutrophils). Functions tested included ROS (dihydrorhodamine 123 (DHR123), phagocytosis of iRFP-expressing Candida albicans, ectodomain shedding (loss of CD62L), and degranulation (increased expression of CD66b). Multiparametric assays were measured on a BD FACS Celesta 4 laser flow cytometer and data was analyzed on FlowJo software. Results Neutrophils co-cultured with MSC had an average viability of 96.3% compared to control neutrophils at 92.15%. Using the multiparametric neutrophil functional assay, neutrophils exposed to MSC ex vivo had increased functional responses to the fungal pathogen Candida albicans. MSC-conditioned neutrophils exhibited a 33.2% increase in degranulation, a 13.4% increase in ROS generation, and 16.7% additional phagocytosis compared to non-MSC neutrophil (control). Compared to fresh neutrophils isolated the day of testing, MSC-conditioned neutrophils had an average increase in phagocytosis, degranulation, shedding, and ROS generation of 36.9%, 62.7%, 50.3%, and 37.8%, respectively. Conclusion MSC increase the functional effector activity of neutrophils in healthy controls, specifically ROS generation, phagocytosis, ectodomain shedding, and degranulation in response to C. albicans. These data raise the possibility of MSC as a novel therapeutic intervention for patients with invasive infections. Disclosures Michael Mansour, MD, PhD, Thermofisher: Grant/Research Support
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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) | 0.000 | 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) | 0.003 | 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 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".