Effect of Tumor Necrosis Factor Alpha Dose and Exposure Time on Tumor Necrosis Factor-Induced Gene-6 Activation by Neonatal and Adult Mesenchymal Stromal Cells
Bibliographic record
Abstract
Tumor necrosis factor alpha (TNF-α) induced protein 6 is a major anti-inflammatory mediator released by activated mesenchymal stromal cells (MSCs). Neonatal MSCs are considered more metabolically active than cells derived from adult tissues, and potentially less heterogeneous. We hypothesized that a TNF-α-activated neonatal MSC population [human umbilical cord perivascular cells (HUCPVCs)] would show an enhanced level of TSG-6 activation compared with adult bone marrow MSCs (BMMSCs). Thus, we stimulated HUCPVCs, and both human BMMSCs (hBMMSCs) and mouse BMMSCs (mBMMSCs) with 1, 10, 50, and 100 ng/mL of recombinant TNF-α over various exposure times. Supernatant, and total RNA, of the cells were collected for measurement of both TSG-6 RNA expression, and secreted TSG-6 protein. To compare gene levels, quantification was done by normalizing the expression levels of TSG-6 to the geometric mean of the three most stable reference genes, out of a cohort of 30 tested genes, using the Pfaffl method. We found that HUCPVCs exhibited both an enhanced and more rapid response to low dose (1 ng/mL) TNF-α exposure resulting in ∼11.5-fold increase in TSG-6 expression within the first 30 min. In contrast, hBMMSCs showed 2-fold increase by 1 h that increased to 9.5-fold with a higher (50 ng/mL) TNF-α exposure for the same time. mBMMSCs showed a two-fold increase after 24 h that was independent of TNF-α concentration. Thus, although TSG-6 expression level varied among donors, both hMSC populations exhibited enhanced TSG-6 upregulation, upon TNF-α stimulation, compared with mBMMSCs. In conclusion, HUCPVCs showed higher sensitivity, and a prompter response to TNF-α stimulation compared with hBMMSCs. Thus, neonatal MSCs may be a stronger candidate population than those derived from adult bone marrow to treat inflammatory diseases.
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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) | 0.001 | 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".